PROINFLAMMATORY AND ANTIINFLAMMATORY PROPERTIES OF HUMAN RECOMBINANT IL-1-BETA DURING EXPERIMENTAL ARTHRITIS IN RATS .2. PERIOD-DEPENDENT EFFECT

The systemic effects of human recombinant Interleukin-1beta (HrIL-1bet a) on hindpaw edema were determined in arthitis induced by human nativ e type II collagen (CII) with muramyl dipeptide (MDP) both injected on day 0. Daily treatment with HrIL-1beta (0.2 mug sc) pretreatment, fro m D-1 (the day before MDP and CII were injected) to D3 significantly d elayed the secondary inflammation in the uninjected left hindpaw, wher eas the same treatment from D6 to D10 at the end of the ''primary'' in flammation, enhanced the volume of the left hindpaw. Treatment from D1 3 to D17 did not affect the ''secondary'' edema in the left hindpaw. T hus, HrIL1beta administration produces pro- or anti-inflammatory effec ts on a developing polyarthritis depending on when treatment is starte d and is most effective as an anti-inflammatory molecule when started at the peak of the the inflammatory reaction, as previously described. In view of these early findings, we have compared the effect of addin g HrIL-1beta along with MDP in the sensitization procedure on the time -course of CII-induced arthritis. No adjuvant effect of HrIL-1beta was observed. On the contrary, HrIL-1beta significantly decreased the sig ns of inflammation in the injected hindpaw during the secondary inflam mation. In addition, the immune response to type II collagen was less in the group receiving HrIL-1beta, maybe because of nonspecific increa se of antigen clearance. On the other hand, the MDP sensitization proc edure enhanced the incidence of CII arthritis and significantly worsen ed the clinical parameters in both primary and secondary inflammations .