An analysis of the role of tumor necrosis factor in the phenotypic expression of actively induced experimental allergic orchitis and experimental allergic encephalomyelitis.

The role of tumor necrosis factor (TNF) was examined in the pathogenesis of actively induced experimental allergic orchitis (EAO) and experimental allergic encephalomyelitis (EAE) in the mouse. The ability of TNF to function as either an adjuvant or to replace pertussigen in eliciting active EAO was examined by treating groups of mice immunized for disease induction with 10 micrograms of recombinant murine TNF at various time points throughout both the induction and effector phases of the disease process. All groups of animals receiving TNF ranging from 2 days before antigen challenge to 26 days postimmunization failed to exhibit significant disease in comparison to animals treated with pertussigen, indicating that TNF can neither serve as an adjuvant nor replace pertussigen in eliciting active disease. Similarly, the role of TNF in the pathogenesis of EAO and EAE was investigated by examining the ability of a known neutralizing rabbit anti-TNF IgG antibody preparation to either inhibit the development or decrease the severity of the clinical symptoms and/or the inflammatory lesions associated with the disease processes. Groups of either B6AF1 hybrid or SJL/J mice were immunized for the induction of active EAO and EAE, respectively. They were passively immunized with either 2 mg of purified anti-TNF IgG or control anti-CFA IgG at time points ranging from 2 days before to 28 days after antigen challenge. All groups, regardless of the day of treatment with anti-TNF IgG, did not exhibit a markedly significant difference in disease outcome in comparison to either groups receiving no antibody or passively immunized with anti-CFA IgG. Taken together, these results suggest that TNF does not appear to be the principal cytokine/lymphokine involved in the pathogenesis of actively induced EAO and EAE.