Objective—To investigate the effects of long-term
administration of recombinant bovine tumor necrosis
factor-α (rbTNF) on plasma glucose and growth hormone
concentrations, and to determine whether
treatment with rbTNF causes insulin resistance in
Animals—5 steers treated with rbTNF and 5 steers
treated with saline (0.9% NaCl) solution (control).
Procedures—In experiment 1, rbTNF (5.0 μg/kg of
body weight) or saline solution (5 ml) was administered
SC daily for 12 days. Blood samples were
obtained before treatment, and plasma was harvested
for determination of glucose, insulin, and growth
hormone (GH) concentrations. In experiment 2,
insulin, glucose, or growth hormone-releasing hormone
(GHRH) was administered IV on days 7, 9, and
11, respectively, after initiation of rbTNF or saline
treatment in experiment 1. Plasma glucose and insulin
concentrations were measured before and at various
times for 4 hours after insulin or glucose administration.
Plasma GH concentrations were measured at
various times for 3 hours after GHRH administration.
Results—In experiment 1, administration of rbTNF
resulted in hyperinsulinemia without hypoglycemia
and decreased plasma GH concentrations. In experiment
2, plasma glucose concentrations were higher
in steers treated with rbTNF and insulin than in controls.
Plasma GH concentrations were lower in steers
treated with rbTNF and GHRH than in controls.
Conclusions and Clinical Relevance—Prolonged
treatment with rbTNF induced insulin resistance and
inhibited GHRH-stimulated release of GH in steers.
Results indicate that rbTNF is a proximal mediator of
insulin resistance and inhibits release of GH during
periods of endotoxemia or infection. (Am J Vet Res 2001;62:794–798)