Investigation of a potential effect of exogenous interleukin 10 on lipopolysaccharide mediated tolerance to lipopolysaccharide in rabbits

Background Postoperative immunosuppression is a risk factor for postoperative infection and sepsis. The lipopolysaccharide (LPS) sensitivity of circulating leucocytes is diminished in the postoperative course. A similar state of LPS tolerance can be induced in the experimental setting by injection of low doses of LPS. This tolerance may be mediated by cytokines which are released following LPS injection. In the presence of interleukin (IL) 10 the LPS‐induced production of numerous cytokines is diminished in leucocytes. The aim of the study was to investigate the effect of exogenous IL‐10 on LPS‐induced tolerance to LPS in rabbits. Methods Rabbits were injected intravenously with LPS 5 μg kg −1 or human recombinant IL‐10 (hrIL‐10) 5 μg kg −1 or with sodium chloride or hrIL‐10 1 h before LPS. Blood was drawn thereafter repeatedly up to the fifth day and incubated without or with LPS (10 ng ml −1 , 1000 ng ml −1 ) for 20 h. Tumour necrosis factor (TNF) α was assayed in plasma supernatants using the L929 bioassay and hrIL‐10 was detected in serum samples by enzyme‐linked immunosorbent assay. Rectal temperature was measured at the indicated time points. Results Injection of LPS transiently (3 days) caused a biphasic fever and a LPS‐tolerant state. IL‐10, like LPS, transiently diminished the capacity for TNF‐α production. The administration of IL‐10 1 h before the injection of LPS neither affected the LPS‐induced suppression of TNF‐α production, nor modified the duration of tolerance. Likewise, fever curves were no different. Conclusion This pilot study shows that, despite IL‐10‐induced reduction of the capacity for (proinflammatory) cytokine production, LPS tolerance following LPS injection was not altered. Thus systemic cytokine production seems not to be responsible for the induction of fever and LPS tolerance. © 2000 British Journal of Surgery Society Ltd