The systemic effects of human recombinant Interleukin-1 beta (HrIL-1 beta) on hindpaw edema were determined in arthritis induced by human native type II collagen (CII) with muramyl dipeptide (MDP) both injected on day 0. Daily treatment with HrIL-1 beta (0.2 microgram sc) pretreatment, from D-1 (the day before MDP and CII were injected) to D3 significantly delayed the secondary inflammation in the uninjected left hindpaw, whereas the same treatment from D6 to D10 at the end of the "primary" inflammation, enhanced the volume of the left hindpaw. Treatment from D13 to D17 did not affect the "secondary" edema in the left hindpaw. Thus, HrIL 1 beta administration produces pro- or anti-inflammatory effects on a developing polyarthritis depending on when treatment is started 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 adding HrIL-1 beta along with MDP in the sensitization procedure on the time-course of CII-induced arthritis. No adjuvant effect of HrIL-1 beta was observed. On the contrary, HrIL-1 beta significantly decreased the signs of inflammation in the injected hindpaw during the secondary inflammation. In addition, the immune response to type II collagen was less in the group receiving HrIL-1 beta, maybe because of nonspecific increase of antigen clearance. On the other hand, the MDP sensitization procedure enhanced the incidence of CII arthritis and significantly worsened the clinical parameters in both primary and secondary inflammations.