The Relationship of Complement Consumption to Immune Fever

Abstract

The administration of cobra venom factor or soluble human serum albumin (HSA)-anti-HSA complexes in antigen excess to rabbits resulted in a lowering of total hemolytic complement and C3 titers which persisted more than 24 hr. When such animals were challenged with complexes made up in 10 times antigen excess, the consumption of complement, febrile and thrombocytopenic responses were significantly diminished from those seen in untreated controls, and the duration of post-challenge leukopenia was shortened. These observations suggest a role for complement consumption, particularly of components C3-9, in the manifestation of these responses. Pyrogenic tolerance to complexes could not be explained by their more rapid removal from the circulation or a failure of the thermoregulatory centers to respond to preformed leukocytic pyrogen, suggesting that impairment in complement consumption either by depletion of C3 or interference with the activation of C1 might be responsible for this state. In contrast to these findings using complexes in 10 times antigen excess, similar prior treatment of immunized rabbits given HSA or of normal rabbits that received a mixture of soluble and insoluble complexes in 3 times antibody excess failed to suppress febrile or hematologic responses. If the formation of antigen-antibody complexes is essential for the production of these responses in immunized animals challenged with specific antigen, it appears that the large, rapidly-cleared complexes formed near equivalence are most likely involved in producing these biologic activities. Whereas some of the properties of these complexes make them more able to fix complement in vitro, it seems unlikely that complement-mediated mechanisms are significantly involved in the pathogenesis of the in vivo responses measured in these investigations.