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A diminished gamma-interferon (IFN-gamma) production by T cells from patients with rheumatoid arthritis (RA) in response to autologous stimulation coincides with a defective regulation of Epstein-Barr virus (EBV) transformation and is in part due to monocyte-produced interleukin-1 (IL-1) inhibitor and prostaglandins. Since IL-2 can act directly on unstimulated T-cells to induce IFN-gamma production we have now examined the effect of recombinant IL-2 (rIL-2) on purified resting T lymphocytes from RA patients. Treatment with rIL-2(25 U/ml) of lymphocytes from 15 controls led to an increased production of 72-h supernatant EBV-inhibitory activity (19 +/- 4% SE without; 48 +/- 7% with rIL-2), but had only minimal or no effect on gamma-interferon production by E-rosetting lymphocytes from 15 patients with active RA. This defect could not be corrected by adding indomethacin to RA cultures.

A case of autoimmunohemolytic anemia following mefenamic acid therapy is described. A free anti-erythrocytic antibody of the IgG class was found in the serum of the patient. The same antibody was also found in the eluate of the patient's red cells. No blood group specificity could be demonstrated. Direct participation of the drug in the antibody red cell reaction could be ruled out by "facilitation" and "inhibition" tests.

The production of human interleukin-1 alpha (IL-1 alpha) in Escherichia coli is described together with a method for its purification. The isolated protein was shown to be pure and physically homogeneous. The in vitro biological activity of IL-1 alpha was tested with the mononuclear-cell factor and the lymphocyte-activating factor assays. The specific activity determined with both assays was about 3 X 10(7) units mg-1 and is similar to that observed with recombinant human IL-1 beta. The purified protein was resolved by chromatofocusing into two species of isoelectric points 5.45 and 5.20 (75% and 25%, respectively, of the total protein). Both species had similar chemical properties and biological activities to the unfractionated protein. The charge difference between the species was attributed to the deamidation of a single Asn or Gln residue.

Neurotransmitters and psychotropic drugs may affect the immune system by direct action on immunocompetent cells or indirectly via hormonal secretions induced by these drugs. The effect of centrally acting drugs (lithium, antipsychotic, antiepileptic, hypotensive and opioid agents) on the immune system is reviewed and the mediator role of hormonal changes is assessed. Clinical implications resulting from these immune modulations are analyzed within the framework of autoimmune, allergic, infectious and neoplastic diseases.

In order to identify factors which may regulate the functions of dermal fibroblasts, cell lysates and conditioned media of cultured human epidermal cells were tested on dermal fibroblasts for the stimulation of prostaglandin E2- and collagenase-production. Both prostaglandin E2- and collagenase-stimulating activities appeared during epidermal cell culture: after 2 d they were detected in the cell lysate, and after 4 d of culture they were found also in the conditioned media. Molecular sieving chromatography of epidermal cell lysates led to the detection of two main peaks showing concomitant prostaglandin E2- and collagenase-stimulating activities at Mr approximately equal to 18 000 and Mr approximately equal to 10 000. A single peak of concomitant prostaglandin E2- and collagenase-stimulating activities were seen at Mr approximately equal to 10 000 in the epidermal cell conditioned media. This suggests that the cell-associated concomitant prostaglandin E2- and collagenase-stimulating activities are processed from a common precursor molecule and released. Collagenase-stimulating activity without accompanying prostaglandin E2 was also detected in the range of Mr approximately equal to 30 000-45 000.

Lymphocytes influence the production of both prostaglandin E2 (PGE2) and interleukin 1 (IL 1) by monocytes. We have examined whether these two products are released concomitantly or not under identical culture conditions using monocyte- and lymphocyte-enriched populations obtained on Percoll gradient. IL 1 was measured as mononuclear cell factor (IL 1/MCF). When incubated with concanavalin A, the monocyte-enriched fraction (MF; 80-91% monocytes), but not the lymphocyte-enriched fraction (LF; 95% lymphocytes) produced increasing amounts of PGE2 and MCF. However, when LF cells were added to MF cells in culture, a 40% to 60% decrease of PGE2 secretion was observed whereas the MCF production remained unchanged or increased up to 26-fold. Such a dissociation between IL 1 and PGE2 production by monocytes indicates independent regulation mechanisms in controlling the immune response under the influence of lymphocytes.

Synthetic calcium pyrophosphate dihydrate crystals and, to a lesser extent, synthetic hydroxyapatite crystals increased the amount of interleukin-1/mononuclear cell factor released by human blood monocytes, as measured by collagenase and prostaglandin E2 production by rabbit chondrocytes, human dermal fibroblasts, and adherent rheumatoid synovial cells. The same crystals also directly induced collagenase and prostaglandin E2 secretion by rabbit chondrocytes, and potentiated the action of interleukin-1/mononuclear cell factor on chondrocytes. These mechanisms may be important in the pathogenesis of the destructive arthropathies associated with these crystals.

Circulating monocytes bind 125I-insulin in a specific fashion and have been used to analyze the ambient receptor status in humans. When freshly isolated circulating monocytes are incubated with 125I-insulin and examined by electron microscopic autoradiography, approximately 18% of the labeled material is internalized after 15 minutes at 37 degrees C. By 2 hours at 37 degrees C, approximately one half of the 125I-insulin is internalized. Internalization occurs also at 15 degrees C but at a slower rate. Furthermore, the monocytes bind and internalize 125I-insulin in a manner that mirrors that of major target tissues, such as rat hepatocytes. These data suggest that the insulin receptor of the circulating monocyte might be regulated by adsorptive endocytosis in a manner analogous to that of target tissue, such as the liver.