Serum TNF alpha in mouse typhoid and enhancement of a Salmonella infection by anti-TNF alpha antibodies

Abstract

Tumour necrosis factor alpha (TNF alpha) was detected by the L929 cell assay in the sera of mice 1 h after large i.v. inocula of virulent Salmonella typhimurium C5. TNF alpha was not detectable in sera from innately susceptible BALB/c mice during the course of a lethal infection commencing from a low inoculum, or from resistant A/J mice during the course of a lethal or sublethal infection, but only 1 h after i.v. challenge with large numbers of organisms. Administration of a single dose of rabbit polyclonal anti-TNF alpha antiserum on day 1 had no effect on the early course of a lethal infection in A/J mice. However, the same treatment exacerbated a sublethal infection in A/J mice. Anti-TNF alpha treatment did not accelerate the early bacterial net growth rate in the RES. Instead, the cfu count in treated mice continued to increase past the point at which the host response suppressed a further increase in bacterial numbers (the plateau phase) in normal controls. A second dose of anti-TNF alpha antiserum on day 4 together with a higher but still sublethal challenge caused a lethal infection in A/J mice. The results indicate that TNF alpha is important in mediating the plateau phase in a salmonella infection, and its effect may be local.