INDUCTION OF ACUTE ARTHRITIS IN MICE BY PEPTIDOGLYCAN DERIVED FROM GRAM-POSITIVE BACTERIA AND ITS POSSIBLE ROLE IN CYTOKINE PRODUCTION

The activities of a water-soluble peptidoglycan fragment derived from Staphylococcus epidermidis (SEPS) were examined as to their role in pr oliferation of spleen mononuclear cells (SMNC) from various strains of mice, the production of cytokines in vitro, and the induction of an i nflammatory reaction in vivo. The proliferation of SMNC from C3H/HeN, C57BL/6, AKR, DBA/2, and ddY mice in reaction to SEPS in vitro showed a peak on day 3 and was greater than that of SMNC from BALB/c mice. Th e cells of SMNC from C3H/HeN mice responsive to SEPS were indicated to be mainly macrophages. A time kinetics experiment showed a coincidenc e in the proliferation of SMNC in reaction to SEPS and the detection o f colony-stimulating factor (CSF) activity. Interleukin 2 (IL-2) activ ity was not detected during the incubation periods. When SEPS was admi nistered to mice, much stronger mRNA transcripts of granulocyte-macrop hage (GM)-CSF were detected in the lungs of C3H/HeN mice than in BALB/ c mice. On the other hand, the amounts of IL-1 and PGE2 produced by SM NC of BALB/c mice stimulated by SEPS were greater than those produced in C3H/HeN mice. SEPS was confirmed to induce arthritis in BALB/c mice , but not in C3H/HeN mice. Our findings suggest that the production of GM-CSF is involved in the in vitro proliferation of SMNC in reaction to SEPS and that along with IL-1 and PGE2 production, contributes to t he inflammation by SEPS in vivo.