Interleukin-1 (IL-1) mediates symptoms of sickness during the host response to infection. IL-1 exerts its effects via several subtypes of receptors. To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL-1RI-/- mice were resistant to the sickness-inducing effects of IL-1beta administered intraperitoneally (2 microg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 microg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL-1RI-/- mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL-1, since lipopolysaccharide-induced expression of brain IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 transcripts were identical in IL-1RI-/- and control mice when measured by semiquantitative reverse-transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF-alpha action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 microg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 microg/mouse) on behaviour in IL-1RI-/- but not in control mice. Since IL-1RI-/- mice were not more sensitive to intracerebroventricularly TNF-alpha (50 ng) than control mice, these results indicate that IL-1RI mediates the sickness effect of IL-1 and that TNF-alpha simply replaces IL-1 when this last cytokine is deficient.

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A new in vitro method was devised to assess the effects of pesticides on honey bee brood. The method allowed the quantification of doses ingested by larvae and the assessment of larval and pupal mortality. Larval mortality in control samples was lower than 10%. Two active substances were tested: dimethoate and fenoxycarb. The LD(50) of dimethoate was 1.9 microg larva(-1) 48 h after oral exposure of larvae at day 4. Additional dose-related effects on pupal mortality were noted. After a chronic intoxication, the NOAEC (No Observed Adverse Effect Concentration) for larval mortality at day 7 was 2.5 mg kg(-1), whereas a NOAEC of 5 mg kg(-1) was found at day 22 for delayed effects on the reduction of adult emergence. Fenoxycarb applied at day 4 showed no effect on larvae, whereas emergence of adults was affected at doses higher than 6 ng larva(-1).