Takashi Katsura

Inflammatory Cytokines and Enzymes in Synovial Fluid of Patients with Rheumatoid Arthritis and Other Arthritides

Cytokines and lysosomal enzymes, which are produced by inflammatory cells, play a role in inflammation. We have found that synovial fluid (SF) in rheumatoid and septic arthritis contained a large number of white blood cells (WBCs) and high levels of cytokines and enzymes, while in contrast the SF of osteoarthritis and traumatic arthritis did not contain significant amounts. Measurements of WBCs, cytokines and enzymes in SF are useful for evaluating clinical disease activity. Assays for WBCs and enzymes are simple and rapid when compared to those for cytokines.

Suppression of pulmonary granulomatous inflammation by immunomodulating agents

We demonstrated previously that macrophages and macrophage-derived cytokines including lymphocyteactivating factors (LAFs) play a critical role in lung granuloma formation in mice and that granulomas sizes correlated with LAF activity in the lesions. In the present study, we examined the effects ofd-penicillamine (d-Pc), 2-acetylthiomethyl-3-(4-methyl-benzoyl)propionic acid (KE-298) and dexamethasone (Dex) on dextran bead-induced lung granulomas in mice. KE-298 is a newly synthesized compound containing sulfur (S) similar tod-Pc. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous lung extracts of the mice contained high levels of LAF that were correlated with granuloma sizes. The lesions and local LAF activity were inhibited by administration of these agents. The most potent inhibitor was Dex. The suppressive effect of KE-298 was similar to that ofd-Pc. These results suggest that suppression of granulomas may be attributed to inhibition of LAF activity/synthesis by these agents.

Desensitization of delayed-type hypersensitivity in mice: suppressive environment.

The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2) activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH) 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.