No abstract

SUMMARY The cytokine response to injury or trauma is of interest in terms of both its mediation of the acute phase response and its possible relation to the immunological depression observed after major surgery. In this study, the production of cytokines IL‐1 β, tumour necrosis factor‐alpha (TNF‐α), IL‐6 and the naturally occurring inhibitor of IL‐1, IL‐1Ra, have been investigated in infants and children undergoing Swenson's pull‐through operation for Hirschsprung's disease. Samples of peripheral blood were taken before, during and after surgery for the measurement of cytokines. IL‐IRa levels increased significantly (P <0.01) at 2 h after commencement of surgery, with maximal levels for individual patients being attained between 3 h and 5 h (range 7.6–67.9 ng/ml). The mean level of IL‐1 Ra was maximal (26.2 ng/ml) at 5 h and returned to baseline levels between 24 h and 72 h. There were no changes observed in the circulating levels of IL‐1β in nine out of 11 patients following commencement of surgery. TNF‐α levels did not increase in any of the patients studied. IL‐6 levels increased significantly (P<0.02) 3 h after commencement of surgery, reaching maximum concentrations at 24 h (range 20–670 pg/ml), with levels falling between 48 h and 72 h. This study demonstrates, in vivo, the independent induction of IL‐IRa without a concomitant increase of IL‐lβ levels after major surgery. It also shows that IL‐1Ra is the earliest cytokine produced in response to surgical stress.

Stimulation of T-lymphocytes with mitogens or antigens results in the production of the cytokine interleukin-2, which exerts its physiological effect by interacting with a specific IL-2 receptor on the cell surface. The alpha-chain of this receptor is induced and expressed on the cell surface after lymphocyte activation. Following continuous antigen stimulation, a smaller soluble form of this alpha-subunit (sIL-2R-alpha) is shed from the membrane of activated cells. This study describes a sandwich ELISA for bovine sIL-2R-alpha that was developed using monoclonal antibodies specific for bovine IL-2R-alpha (CD 25). The feasibility of using sIL-2R-alpha released by activated T-lymphocytes as an in vitro marker of cell-mediated immunity (CMI) in cattle is demonstrated. Calves were immunized with the foreign protein keyhole limpet haemocyanin (KLH) and the development of CMI was followed using sIL-2R-alpha release, IFN-gamma production and lymphocyte proliferation assay. The results showed that the release of sIL-2R-alpha by previously sensitized cells following stimulation with antigen is likely to be a useful marker of CMI in infectious diseases, and in the study of T cell antigens and/or novel vaccines. Using appropriate detection systems, the measurement of sIL-2R-alpha may also prove to be a useful marker of CMI in other species.