Search

Ability of Sugi basic protein (SBP)-pullulan conjugate to elicit the Arthus reaction was found to be markedly reduced, about 100 times lower than that of native SBP. To analyze this reduced ability, activation of complement by immune complex consisting of SBP-pullulan and anti-SBP antibodies was studied. Tests for complement consumption, C3 conversion and cleavage of factor B revealed that immune complex formed with SBP-pullulan is incapable of supporting efficient activation of the complement system. Previously, we have shown data suggesting that SBP-pullulan conjugate would be a good candidate for desensitization therapy against cedar pollinosis. The results presented in this paper provide additional support for the suggestion.

The purpose of this report is to present results demonstrating for the first time the development of rheumatoid factors to rabbit IgG-Fc as well as antirabbit F(ab')2 antibodies in guinea pigs after chronic sensitization with purified native type II bovine collagen. The sensitized animals also developed antibodies to guinea pig Ig. Antibodies to rabbit Ig arose as early as 3 weeks after bovine type II collagen injection and persisted for as long as 80 weeks when the experiment was terminated. The anti-Ig antibodies did not cross-react with the type II bovine collagen. Despite development and persistence of higher titers of RF and anti-F(ab')2 antibodies in the immunized animals, the animals failed to show clinical evidence of inflammatory polyarthritis. These results indicate that rheumatoid factors as well as antibodies to F(ab')2 arise independently of the clinical expression of disease.

Footpad reactions elicited in DHS mice using human γ-globulin (HGG)-coated polystyrene latex particles and soluble HGG (sHGG) were compared. Both the magnitude and the persistence of DHS lesions produced by HGG-latex were considerably greater; at 24, 48 and 72 h after challenge, the level of reactivity induced by HGG-latex was 24, 41 and 71% higher, respectively, than those elicited with sHGG. Early nonspecific swelling following injection of HGG-latex in footpads of normal mice was negligible by 24 h, whereas Arthus-responsive animals did not return to control levels until 48 h. The possible advantages and limitations of using particle-associated protein to elicit DHS reactions are discussed.

Footpad assay of delayed-type hypersensitivity to bovine serum albumin (BSA) was studied. Injection of saline solution of BSA (S-BSA) into footpads of sensitized mice resulted in the development of only the local Arthus-type reaction. Injection of alumprecipitated BSA (AP-BSA), however, was effective in generating both Arthus- and delayed-type reactions. The difference between S-BSA and AP-BSA in the ability of elicitation of delayed-type reaction may be attributable to the difference in the retention of these two forms of antigen in the footpad, since S-BSA was found to be eliminated much more rapidly from footpads than AP-BSA.

The effects of PRD-92 Ea were examined on the increased plasma protein extravasation in the skin of guinea pig and rat elicited by specific antigens and spasmogenic mediators. PRD-92 Ea was found to be a potent inhibitor of rat PCA reactions when administered intradermally, intravenously or orally. This compound did not antagonize the local inflammatory responses of histamine, bradykinin or 5HT. This implies that in vivo PRD-92 Ea acts predominantly as an anti-allergy agent rather than a spasmogen antagonist. At high concentrations PRD-92 Ea directly increased vascular permeability when injected intradermally (greater than 250 micrograms/site) or administered by aerosol into the lung (greater than 10%). The importance of investigating such direct irritant actions of similar new drugs is discussed.

The effect of 4 immunosuppressive agents – hydrocortisone (HC), cyclophosphamide (CY), azathioprine (AZ) and methotrexate (MTX) – on cutaneous delayed-type hypersensitivity (DTH) and Arthus reactions to the intradermal injection of ovalbumin (OA) in rats sensitized to OA in Freund’s complete adjuvant (FCA) was studied. Multiple doses (daily for 4 days) were given either early, beginning on the day of sensitization, or late, beginning 9 days after sensitization. Single doses were given on the day of challenge with OA. All late multiple doses of drugs except HC depressed the DTH at 24 h in the following order of decreasing magnitude: MTX, CY, AZ. The DTH at 24 h was depressed by early multiple doses of MTX at all doses, by CY at all but the lowest dose, and by AZ at the intermediate dose; HC had no effect. When the drugs were given as single late doses, only CY at the lowest dose and MTX at the higher doses effectively (depressed the DTH at 24 h. Increased Arthus reactions occurred after early and late multiple doses of HC and after a late single dose of CY at the highest dose. After late multiple doses the Arthus reaction was unaffected by either CY or MTX but was depressed by all doses of AZ. HC administered as 3 injections around the time of challenge markedly depressed the delayed and Arthus reactions. These results show that each of the 4 immunosuppressive drugs could depress DTH and Arthus reaction to OA, but the degree of depression varied with the time of drug administration relative to sensitization and challenge, and the dose of drug used. Histologic examination of skin test sites showed that an apparently negative reaction did not necessarily imply total absence of a cellular inflammatory response.

The F1 generation, produced by mating Wistar rats from the Tuck colony which react to dextran (R rats) with Wistar rats from the NELP colony which do not react (NR rats) all responded to dextran with an anaphylactoid oedema reaction, and developed arthritis after adjuvant injections (AIA), but failed to show ovalbumin-induced delayed hypersensitivity reactions (OA) and experimental allergic encephalomyelitis (EAE). Back-crossing the F1 generation with NR rats produced animals, only half of which responded to dextran, though all the offspring reacted well to AIA, but poorly to OA and EAE. This confirms that resistance to AIA is not associated with resistance to dextran.

Weight determination of replicas of the feet from living mice is described as a new method for evaluating the degree of the experimentally induced foot pad swelling in immunized mice. The new method gives objective, well documentable results and offers advantage to the commonly used assay with the dial calliper gauge when there is need for a good documentation or whenever there is a large number of animals to be tested within a narrow time margin.

Carrageenan, a high molecular weight, sulfated polygalactose known to be toxic for macrophages in vitro was utilized in in vivo experiments to further study the role of this cell type in the initiation and expression of delayed hypersensitivity. When administered intraperitoneally to sensitized guinea pigs around the time of skin testing, carrageenan suppressed the expression of existing delayed hypersensitivity reactions to BSA. In addition, when administered at the time of immunization, carrageenan suppressed the development of subsequent delayed hypersensitivity. Carrageenan, in vitro did not appear to be cytotoxic for lymphocytes either structurally or functionally. It did not possess mitogenic properties and did not interfere with phytohemagglutinin induced lymphocyte transformation.