INDUCTION OF A PROINFLAMMATORY CYTOKINE NETWORK BY MYCOPLASMA ARTHRITIDIS-DERIVED SUPERANTIGEN (MAS)

Mycoplasma arthritidis is an arthritogenic organism for rodents, produ cing a superantigen (MAS), It has been postulated that mycoplasmas or superantigens thereof might play a role in human rheumatoid arthritis, Since M. arthritidis fulfills both, the present study was performed t o investigate MAS-specific cytokine induction, Human or murine leukocy tes were stimulated with MAS, staphylococcal enterotoxin E (SEE), or l ipopolysaccharide (LPS). Cytokines were measured by ELISA, Bioassay, a nd RT-PCR, The response to MAS in humans was individually restricted, in contrast to the response to SEE or LPS. Furthermore, MAS showed the same capacity for inducing proinflammatory cytokines as interleukin ( IL)-1 IL-6, and IL-8 as SEE and LPS, However, MAS showed a significant ly decreased capacity to induce the anti-inflammatory cytokine IL-10 a nd IL-1RA, In mice, the reactivity to MAS was strictly MHC-II restrict ed, in contrast to that of SEE or LPS. The individual response to MAS in humans might be explained by the difference of the HLA-DR haplotype because H-2-differing mouse strains showed the same discrepancies, MA S induced an overproduction of proinflammatory cytokines, when its abi lity to induce proinflammatory and anti-inflammatory cytokines was com pared with those of SEE and LPS, The individual response may explain a n MHC linkage, and the failure to induce anti-inflammatory cytokines m ay be the reason for a chronic disease in contrast to acute inflammati on.