Search

In a multicenter, placebo-controlled and randomized double-blind trial 119 patients with rheumatoid arthritis were treated with thymopentin, an immunoregulating drug. The data of 107 patients were complete enough to be evaluated: 51 were given intravenous injections over ten minutes of 50 mg thymopentin three times weekly, 56 were similarly treated with a placebo solution. Significant improvement of five among nine clinical criteria were obtained with thymopentin after the third week of treatment. The response rate (improvement of a clinical parameter by at least 40%) was significantly greater for all clinical parameters in the thymopentin group. Regression to a functionally more favourable class (Steinbrocker's classification) occurred in seven thymopentin-treated, but in none of the placebo-treated patients. The improvement gradually subsided over four weeks after the end of treatment. There were no changes during the trial with respect to immunological, biochemical or haematological findings. Except for one systemic allergic reaction there were no side effects.

Objective To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). Methods In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. Results After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate vs no drug-related deaths among the subjects receiving leflunomide. Conclusions Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.

To identify genes that contribute to the manifestation of rheumatoid arthritis we performed association studies via microsatellite analyses of immunorelevant loci (HLA-DRB, 5 T cell receptor loci, TNFa IL1, IL2, IL5R and CD40L). A total of 183 patients and 275 healthy controls were typed in terms of HLA and grouped according to the known predisposing HLA-DRB1 genes (DRB1*04; relative risk approx. 5; DRB1*01, relative risk approx. 2; a third group carried neither allele). Microsatellite polymorphisms characterizing the TCRBV6S3, CD3D, IL1A, IL2, and IL5R genes did not show significant associations with rheumatoid arthritis, whereas TCRBV6S1, TCRBV6S7, TNFa, and CD40L genes may influence relative protection or risk in certain groups of patients. Analysis of a microsatellite marker adjacent to the transcription element alpha (TEA) in the T cell receptor alpha delta complex indicates that in the cohort carrying neither the DRB1*04 nor the DRB1*01 allele the relative risk to acquire rheumatoid arthritis is increased (13) or decreased (0.07), depending on the inherited microsatellite allele adjacent to the TEA locus. Sequence analysis of the closely linked TEA region from patients and controls revealed a novel dimorphism. Only the newly identified TEA allele leads to binding of a nuclear protein that may be involved in the regulated expression of the TCRDA genes. Subsequent typing of rheumatoid arthritis patients and controls revealed, however, that the association of the microsatellite marker is largely independent of the TEA allele, confirming incomplete linkage in the 2 kb region of the TCRDA locus. These results are discussed in the context of hot spots of recombination in this genomic region and other linked candidate sequences that predispose to develop rheumatoid arthritis.

The efficacy and tolerability of pyritinol (PY) and auranofin (AU) were compared in a multicentre double-blind study. Patients with RA received 600 mg/day PY or 6 mg/day AU for 1 year. Response was rated by a defined improvement in at least four of the following: Ritchie index, joint swelling index, rating scales for pain and general well-being, functional index, morning stiffness, ESR. Of the 139 fully evaluable PY patients 61 (44%) dropped out due to adverse events or response failure compared with 44 (31%) of the 142 AU patients. In patients treated for 1 year efficacy parameters improved more in the PY than in the AU group, with significant differences for the general well-being (P = 0.022), ESR (P = 0.029) and haemoglobin (P = 0.0042). The response rate for PY (61/78 patients, 78%) was significantly superior to AU (58/98 patients, 59% P = 0.009). An intention-to-treat analysis corroborated this result (P = 0.030). Adverse events (AE) occurred in 64% of PY patients and in 58% of AU patients: main AE were mucocutaneous symptoms (PY 36%, AU 23%) and gastrointestinal complaints (PY 30% AU 37%). Single cases of proteinuria, hepatic and haematological abnormalities were noted in both groups.

The controlled clinical trial reported here is part of a multicenter clinical and basic research project, sponsored by the German Federal Minister of Science and Technology, directed by a standing commission of the president of the Max-Planck-Gesellschaft, and coordinated by the Max-Planck-Institut fur Biochemie, Munchen. Overall, 249 patients with rheumatoid arthritis (RA) were enrolled by 16 participating hospitals. In addition to NSAID treatment, patients were randomly given either interferon gamma (IFN-γ) or placebo. In the IFN-γ group, 107 patients were evaluated and in the control group, 116 patients were evaluated. The response rate after 3 months of treatment, according to joint pain indexes, was significantly higher in the IFN-γ group with an error probability of 1%. IFN-γ was able to reduce the quantity of corticosteroids administered. Compared with the control group, the IFN-γ group benefited considering all parameters measured. Most important side effects were transient fever and transient influenza-like symptoms; all other adverse events were comparable in both groups.

In der schier unendlichen Diskussion um alternative Heilmethoden stehen sich beide Lager haufig wie Kriegsparteien gegenuber [1]. Eine weitgehend vollstandige Auflistung zweifelhafter, nicht allgemein anerkannter oder gesichert nutzloser therapeutischer Verfahren in der Rheumatologie, wie sie von der Kommission „Qualitatssicherung“ ursprunglich beabsichtigt war, erwies sich aus mehreren Grunden als nicht durchfuhrbar. Wir haben uns daher entschlossen, an diese Stelle einen Kurzkommentar in Thesenform zu setzen.

To evaluate the efficacy and safety of meloxicam, a new acidic enolic nonsteroidal anti-inflammatory drug, at doses of 7.5 and 15 mg once daily in patients with rheumatoid arthritis (RA).Meloxicam 15 and 7.5 mg daily was administered for 21 days in this double blind, randomized, placebo controlled study. 159 patients received meloxicam 7.5 mg, 162 received meloxicam 15 mg, and 147 received placebo.Meloxicam 15 mg once daily was significantly superior (p0.05) to placebo in 3 of the 4 primary endpoints (disease activity assessed by the investigator, disease activity assessed by the patient, and reduction of the number of tender/painful joints). No difference was observed regarding number of swollen joints. The difference between meloxicam 7.5 mg once daily and placebo reached statistical significance in 2 of the 4 primary endpoints, disease activity assessed by the patient and number of tender/painful joints. A statistically significant difference between meloxicam 1.5 mg and 7.5 mg was not observed for any primary endpoint. The rating of global tolerance by investigators and patients at the end of the study was similar in the 3 treatment groups, indicating that meloxicam and placebo were generally similarly well tolerated. However, there was a slightly higher incidence of gastrointestinal (GI) disturbances reported by patients receiving meloxicam 15 mg. GI adverse events were reported by 11, 11, and 16% of patients in the placebo, meloxicam 7.5 mg, and meloxicam 15 mg groups, respectively. None were serious.Meloxicam in daily doses of 7.5 and 15 mg is effective in treating the signs and symptoms of RA.

The efficacy and tolerability of pyritinol (PY) and auranofin (AU) were compared in a multicentre double-blind study. Patients with RA received 600 mg/day PY or 6 mg/day AU for 1 year. Response was rated by a defined improvement in at least four of the following: Ritchie index, joint swelling index, rating scales for pain and general well-being, functional index, morning stiffness, ESR. Of the 139 fully evaluable PY patients 61 (44%) dropped out due to adverse events or response failure compared with 44 (31%) of the 142 AU patients. In patients treated for 1 year efficacy parameters improved more in the PY than in the AU group, with significant differences for the general well-being (P = 0.022), ESR (P = 0.029) and haemoglobin (P = 0.0042). The response rate for PY (61/78 patients, 78%) was significantly superior to AU (58/98 patients, 59% P = 0.009). An intention-to-treat analysis corroborated this result (P = 0.030). Adverse events (AE) occurred in 64% of PY patients and in 58% of AU patients: main AE were mucocutaneous symptoms (PY 36%, AU 23%) and gastrointestinal complaints (PY 30% AU 37%). Single cases of proteinuria, hepatic and haematological abnormalities were noted in both groups.

Introduction of a new therapeutic regimen into clinical use should be supported by knowledge of the mechanisms of the pathophysiological conditions to be treated or by an explanation of the pharmacotherapeutic intervention to be offered. In the case of interferon-gamma and its introduction into the therapeutic regimens of rheumatoid arthritis in about 1983, both of these standards of classical pharmacotherapy were missing. Very little was known about the pathophysiology of rheumatoid arthritis, and interferon was known rather as an activator of inflammatory and immunological reactions (for review see [1, 9, 10, 16, 21, 23]). Thus it was rather alarming to rheumatologists when the first anecdotal reports from tumor centers raised the attention of the popular news media: patients suffering from tumors and treated with interferon-gamma claimed improvement of concomitant “rheumatic problems” when exposed to interferon-gamma (O. Klein, K. Wilms, personal communications).

Results of a large therapeutic trial of interferon-gamma in patients with rheumatoid arthritis (RA) are described. Of 110 RA-patients enrolled in this clinical trial, 46 were treated with interferon-gamma for 12 months. During the treatment period, dosage was reduced on an individual basis. There was a correlation between the improvement of clinical parameters, such as pain or morning stiffness, and the improvement of laboratory parameters such as erythrocyte sedimentation rate, anemia, leucocytosis or thrombocytosis. Interferon-gamma was well tolerated, and no organ toxicity was detected.

In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times.

The effect of prednisolone and non-steroid anti-inflammatory drugs on PMNL (polymorphonuclear leucocytes) oxidative metabolism was quantified with a newly standardized NBT test, and it was investigated whether these effects correlate with phagocytosing capacity of PMNL. Prednisolone inhibits NBT reduction in dose dependency already at concentrations, which do not interfere with phagocytosis. Thus prednisolone dissociates phagocytosis and phagocytosis-associated oxidative metabolism. High doses of prednisolone also inhibit phagocytosis. These effects of prednisolone are still demonstrable when PMNL are washed after pre-incubation with the drug. The non-steroid anti-inflammatory drugs (indomethacin, phenylbutazone and pyrazinobutazone) inhibit phagocytosis and NBT reduction at equivalent doses. When PMNL are washed after incubation with the drugs, they regain normal capacity to phagocyse and to reduce NBT. It is suggested that these drugs inhibit phagocytosis directly, and consequently the phagocytosis-associated oxidative metabolism is suppressed.

The kinetics of the reactive cell clones after primary and secondary immunization with SRBC1) modified by cyclophosphamide and a newly synthesized cyclophosphamide analogue 036.5122 (Asta), have been studied. After primary immunization, both substances caused a severe and dose dependent depletion of 19 S PFC2). The 7 S PFC in the late primary response were only slightly inhibited by cyclophosphamide in low dose ranges, indicating, that sensitization could not be prevented by this substance. In contrast, 0.36.5122 was fully able to suppress 7 S PFC. Thus, treatment with 0.36.5122 after primary immunization can fully prevent the expression of the specific response. Experiments dealing with inhibition of a secondary immune response revealed that both test substances were able to strongly suppress the 19 S as well as the 7 S PFC. In general, 036.5122 demonstrates a higher suppressive potency, and the timing of its application for optimal suppression is less delicate than that of cyclophosphamide. 036.5122 was equally well inhibitory, whether given directly before or after antigenic challenge. The hypothesis is discussed, whether the immunosuppressive effect of 036.5122 given before antigenic challenge in the secondary immune response is due to cytotoxic damage of antigen reactive clones stimulated by persisting antigen.

Two alkylating (cyclophosphamide and 036.5122 Asta) and two antiproliferative agents (6-mercaptopurine and azathioprine) have been compared for their immuno-suppressive potency on the primary and secondary humoral immune response of mice. If equitoxic dosages of the respective drugs are compared, the alkylating agents proved to be of much higher immunosuppressive potency than the antiproliferative agents. In non toxic dosages alkylating agents were able to completely inhibit a primary or secondary immune response, whilst a similar effect with antiproliferative drugs could not be obtained even within toxic dose ranges. Induction of immunological tolerance was possible only by use of the alkylating agents. The significance of these comparative studies is discussed in view of the frequent use of the tested drugs in clinical immunosuppression.

Der Crithidia luciliae-Immunfluoreszenztest (Cl-IFT) zum Nachweis von Antikorpern gegen doppelstrangige DNA (ds DNA) wurde in der Diagnostik und Verlaufsbeurteilung des systemischen Lupus erythematodes (SLE) in seiner Wertigkeit mit der radioimmunologischen Bestimmung im Farr-Test verglichen. Es zeigte sich, das der Cl-IFT lediglich bei Patienten ohne Zeichen von Krankheitsaktivitat von geringerer Sensitivitat ist, in Phasen von klinischer Krankheitssymptomatik dem Farr-Test jedoch gleichwertig ist. Eine Ubereinstimmung beider Testverfahren bestand in 76,9% der untersuchten Patienten-Seren; fehlende Ubereinstimmung war nicht nur eine Frage der Sensitivitat, in einigen Seren konnten nur mit dem Cl-IFT Antikorper nachgewiesen werden.

The case history of a 9 months old infant with hepatosplenomegaly, pancytopnaenia and disturbances of clotting and cellular immune reactivity is reported. The spleen was removed and showed striking erythrophagocytosis by proliferating histiocytes, typical of "familial erythrophagocytic reticulosis" (Farquhar). A graft-versus-host reaction is discussed as a possible underlying cause. The favourable clinical course and full recovery point to an interrelation with primary hypersplenism.

Two of three brothers with the classical signs of ataxia telangiectasia were investigated for their immunological disorders at the ages of 13 and 16 years, respectively. The elder brother also suffers from autoimmune hemolytic anemia, a complication which has not yet been described in the course of ataxia telangiectasia. Immunological investigations made in both brothers showed a reduction in the number and function of T lymphocytes. The number of B lymphocytes was normal, among which there were cells staining for IgA, although serum IgA was absent. It seems possible that this phenomenon is caused by a disturbance in the process of maturation of lymphoid cells with a lack of differentiation into IgA-synthesizing plasma cells.

In thirty-two patients with nephrotic syndrome (NS) phytohemagglutinin (PHA)-induced lymphocyte proliferation was studied at various stages of the disease. We demonstrated that lymphocyte transformation during acute exacerbation is markedly decreased, especially if cells are cultured in patient serum. During treatment with steroids PHA-stimulation improves. During full remission all patients showed their maximal lymphocyte stimulation. On the basis of these results and reports from the literature we postulate that patients with the NS have a T cell clone which inhibits the transformation capacity of the remaining lymphocytes through production of a heat stable serum factor. The same or a second factor produced by these lymphocytes could at the same time exert a toxic effect on the glomerular basement membrane.

By the aid of two alkylating agents (cyclophosphamide (CP) and 036.5122, (Asta), applied after a single dose of antigen, tolerance to sheep red blood cells (SRBC), has been induced in NMRI mice. Duration and characteristics of recovery were followed by a second antigenic challenge at various time intervals and by determination of 19 S and 7 S plaque-forming cells (PFC) 4 days later. During recovery from the tolerant state two phases of responsiveness could be differentiated: an early phase with no or markedly reduced numbers of total PFC, all of them being of the IgM type; a later phase with a steady increase in total PFC up to normal values, paralleled by an increase in the proportion of 7 S PFC finally reaching 90% of total PFC. In comparison with CP, recovery from tolerance induced by equitoxic doses of 5122 were delayed and modified. Even after 8 weeks, total PFC to SRBC were still depressed, and the ratio 19 S/7 S PFC resembled neither a typical primary nor secondary pattern. It is concluded that CP-mediated immunological tolerance is followed spontaneously by the establishment of a memory state. This observation, in agreement with findings of other authors, is interpreted as the expression of an established B cell memory compartment during the period of deficient T cell activity. The long-lasting modification of specific responsiveness after 5122 indicates a profound disturbance of the potency to recover from the impact of this alkylating agent, the biological base of which is as yet unidentified. It is suggested that observation of the characteristic features during the recovery phase from tolerance may help to clarify the nature of the defect in specific responsiveness.

In phagocytic cells nitroblue tetrazolium (NBT) is reduced to formazan. This, in turn, is deposited as a dark blue precipitate in the cytoplasm. Stimulation of the hexosemonophosphate (HMP) shunt leads to increased reduction of NBT. Changes in reduction capacity can be quantitated by the extraction and photometrical evaluation of formazan. Data presented here demonstrate that quantitative evaluation of intracellular formazan is a sensitive indicator for mediators of cellular immunity (MCI) activating marcophages. The NBT reduction potential was increased by a factor of 3.7 if bovine γ globulin (BGG) immune peritoneal exudate (PE) cells were incubated with BGG or if MCI-rich culture supernatants were transferred to normal PE cells. The increased NBT reduction was always paralleled by increased inhibition of capillary migration and by positive skin testing. These experiments suggest that the test for NBT reduction may be a quantitative evaluation of MCI activity.

We compared measurements of chemiluminescence (CL) assessing the rate of production of oxygen intermediates at a given instance, and of nitro blue tetrazolium (NBT) reduction detecting total superoxide produced during the assay period, for the assessment of the respiratory burst of both human monocytes (M phi) and polymorphonuclear leukocytes (PMN). In the CL experiments, opsonized and non-opsonized zymosan was used to stimulate peripheral blood M phi and PMN. Opsonized zymosan yielded an earlier and 2-fold higher peak response than non-opsonized zymosan. The stimulatory action of zymosan in CL varied with the time of incubation and depended on the concentration of cells and zymosan. No light generation was observed in the absence of viable cells. In contrast to NBT reduction, incubation of PMN with dextran sulfate did not result in increased light generation but rather in a quenching of the response in CL. Opsonized zymosan also yielded a higher level of NBT reduction than non-opsonized zymosan. Comparing NBT reduction with CL in 21 healthy individuals, with 2 X 10(5) M phi and 2.5 X 10(5) PMN for NBT and 5 X 10(5) PMN for CL tests, we found that NBT brings about spontaneous oxidative metabolism, possibly reflecting the intracellular compartment, the chemiluminescent response of resting cells being only marginal. The data suggest higher sensitivity of the CL method. These results provide useful comparative data for 2 established methods used to document the respiratory burst in phagocytic cells.

Synovial fluid (SF) and synovial fluid mononuclear cells (SFM) were obtained from patients with rheumatoid arthritis (R.A.). The SF stimulated normal blood monocytes for nitroblue tetrazolium (NBT) reduction and inhibited normal lymphocyte response to PHA. Similar activities were found in supernatants from the cultures of SFM cells. Molecular weight of the lymphocytes inhibitory factor(s) produced by SFM was in range 50,000 to 100,000. The factor exerted its inhibitory activity via monocytes and had no direct toxic or blocking effect on lymphocytes. Monocytes played an active role in suppression presumably via production of a second-step inhibitory signal(s). It is suggested that the monocytes activated by the SFM-produced factor(s) are in turn triggered on for suppression of lymphoproliferation. These studies implicate that the state of monocyte activation is important in the regulation of lymphocyte responsiveness. This model of suppression may provide some explanation for SF lymphocyte hyporeactivity to mitogens in R.A.

By means of cobra venom factor (CVF) it is demonstrated that the stimulation of hexosemonophosphate shunt (HMPS) of human polymorphonuclear leukocytes (PMN) by zymosan (Z) and dextran sulfate (DS) is caused by at least two modes of activation: (a) via activation caused by phagocytosis, (b) via activated alternative pathway of complement activation (APC). Active factors of APC presented with phagocytizable objects strongly enhance activation of PMN. The effect of APC can be observed in serum-containing as well as in serum-free cultures. It can be demonstrated that in serum-free cultures the factors of APC participating in the activation of PMN are supplied by monocytes. By the use of synthetic hexapeptide (HP) representing the COOH-terminal sequence of human C3a further evidence is provided that factors of APC are able to activate the PMN.

The new concept of first level and second level lymphatic organs, and the fact that all first level lymphatic organs defined so far are lymphoepithelial, justifies a new close look at all types of lymphoepithelial relationships. In this investigation the life span of lymphocytes within different epithelia of mice have been studied with the aid of continuous labelling with H3-thymidine and subsequent autoradiography. The majority of the lymphocytes within the jejunal epithelium seems to be short-lived. About half of the lymphocytes within the epithelium covering Peyer’s patches and in epidermis also seem to be short-lived, while the other half is long-lived. Most of the liver lymphocytes seem to be long-lived, as are the blood lymphocytes. The results are discussed in the light of other recent findings about lymphocytes within epithelia, which we have called theliolymphocytes.

For treatment of diseases such as rheumatoid arthritis or systemic lupus erythematodes, which are initiated or sustained by immune-pathological mechanisms, various "immunosuppressive" drugs are used. There are conflicting data as to the benefit of this type of therapy. In this paper it is attempted to define a base for a more differentiated application of available drugs, since the present therapeutic approach seems rather empiric or is deducted from analogy to selected animal experiments. The investigations presented focus primarily on the behaviour of the small and medium lymphocytes of the organism, the adopted carriers of immunological (as well as autoimmune) reactivity, under conventional conditions (and under the influence of suitable drugs) as a biological supposition for the activity of "immunosuppressives". In rabbits, and mice, number and rate of proliferation of lymphoid cells is determined in untreated controls and animals treated with 6-mercaptopurine (6-MP) and cyclophosphamide (Cy), two immunosuppressive agents representing different types of pharmacological action. The elucidation why in rabbits both substances are equally immunosuppressive, whereas in mice only Cy has significant immunosuppressive activity, yields the base for a therapeutic concept of clinical immunosuppression. This species dependent activity of 6-MP can be explained by different proliferation kinetics of lymphoid cells in mouse and rabbit. Lymphocytes of the rabbit, compared to those of mice, are short-lived and have a distinctly higher proliferation rate. Thus, 6-MP, as an antiproliferative agent, leads, in the rabbit (under long-term as well as single-dose therapy) to a significant reduction of the number of small lymphocytes, whereas it reduces the long-lived lymphocytes of the mouse only marginally, thus explaining the good immunosuppressive potency in the rabbit and failure in the mouse. Cy leads, in both species, to a marked reduction of small lymphocytes and affects the long-lived cells of the mouse as well, resulting in high immunosuppressive potency in both species. In the NZB mouse, a well-fitting model of human lupus erythomatodes, Cy is successful in prophylaxis and therapy. A similar therapeutic effect cannot be obtained with 6-MP. Neither of the two groups of substances revealed selective activity on circulating T- or B-cells. According to the literature available, lymphocytes in humans are predominantly long-lived, too. Accordingly, Cy possesses a good immunosuppressive potency in man, too. Its therapeutic success is paralleled by a reduction of small lymphocytes. In conclusion, a true basic immunosuppressive therapy of autoimmune diseases in humans will primarily be possible by aid of substances which act through a cytotoxic mechanism and are thus able to affect even the long-lived human lymphocytes. In contrast, a substance acting purely through interference with certain steps of cell proliferation will predominantly remain restricted to an antiphlogistic use.

SUMMARY We studied the respiratory burst activity of peripheral blood monocytes and polymorphonu clear leukocytes (PMN) in eleven patients with psoriasis and eleven healthy controls, using zymosan particles to activate the phagocytes in vitro. The activation of the phagocytes was measured in a luminol-enhanced chemiluminescence (CL) assay. We found a significantly higher respiratory burst activity of both monocytes and PMN in patients with psoriasis compared with the control subjects. The percentages of monocytes in psoriatics did not differ from those of the controls. The higher amount of zymosan-induced CL activity generated in the patient group was unrelated to the age of the individual. Our data indicate increased metabolic reactivity of both monocytes and PMN in psoriasis.

Antinuclear factors in serum were determined in 37 patients with acute and 50 with chronic pancreatitis. Of the 5 with acute pancreatitis of unknown etiology, 4 had serum antinuclear factors in high titers; of the 16 with chronic pancreatitis of unknown etiology, 10 had serum antinuclear factors in high titers and 4 in low titers.

In the course of allergic encephalomyelitis (EAE) in chickens, azimexone suppressed the production of the specific IgM immunoglobulins. Moreover, it decreased the level of haptoglobin and sialic acid but stimulated the activity of antitrypsin. It was also observed to reduce the production of the plasmatic cells in the spleen. L-cysteine hydrazide hydrochloride decreased the level of sialic acid in EAE; intensified the activity of trypsin inhibitor and exerted no effect upon the level of antimyelin antibodies.

We tested whether highly purified human β1H and C3b, two proteins of the alternative pathway of complement activation, could exert an influence on the activity of human monocytes (Mφ). The activation process of Mφ was assessed by measurements of the respiratory burst in terms of nitro blue tetrazolium (NBT) reduction and by chemiluminescence (CL) tests. In NBT reduction experiments, we found a tendency for β1H to increase NBT reduction, while C3b was found to be rather inhibitory. In CL measurements, both β1H and C3b displayed a stimulatory effect on Mφ, showing different time- and dose-dependency. For β1H, the maximum stimulation occurred after 15 min, whereas for C3b after 45 min. Zymosan particles which served as a positive control also showed the highest stimulation after 45 min. In dose—response experiments, β1H reached a plateau ranging from 30 to 80 μg/ml. In contrast, using C3b up to 170 μg/ml, no plateau was reached. Mφ-depletion and enrichment studies suggested at Mφ as being responsible for the stimulatory effects found.