Comparison of the feeding responses to bacterial lipopolysaccharide and interleukin-1 beta.

To further investigate the idea that endogenous interleukin-1 plays a major role in the anorectic effect of bacterial lipopolysaccharide (LPS), feeding responses to recombinant human interleukin-1 beta (rhIL-1 beta) and LPS, as well as crosstolerance or -sensitization between both compounds, were investigated in rats. Intraperitoneally (IP) injected paracetamol (50 mg/kg body weight = b.wt.) markedly attenuated the anorectic effect of rhIL-1 beta (50,000 LAF units/kg b.wt., IP), but was clearly less effective in attenuating the anorectic effect of LPS (100 micrograms/kg b.wt., IP). As in previous experiments of ours, repeated IP injections of rhIL-1 beta (three injections of 50,000 LAF units/kg b.wt. on experimental days 1, 4, and 10) resulted in sensitization to the anorectic effect rhIL-1 beta, whereas repeated IP injections of LPS (three injections of 100 micrograms/kg b.wt. every second day) resulted in LPS-tolerance. Sensitization to the anorectic effect of rhIL-1 beta did not affect the anorectic response to LPS. Likewise, LPS-tolerance did not alter the anorectic response to rhIL-1 beta. RhIL-1 beta suppressed feeding by reducing meal frequency and meal size. In contrast, the anorectic effect of LPS was due entirely to a reduction of meal frequency. The results indicate that rhIL-1 beta and LPS do not affect feeding through exactly the same mechanism.