Prevention of Jarisch–Herxheimer Reactions by Treatment with Antibodies against Tumor Necrosis Factor
Daniel Fekade, M.D., Kyle Knox, M.B., Kebede Hussein, M.B., Amsel Melka, M.B., David G. Lalloo, M.D., Ruth E. Coxon, F.I.M.L.S., and David A. Warrell, D.M.
Background In patients with louse-borne relapsing fever (Borreliarecurrentis infection), antimicrobial treatment is often followedby sudden fever, rigors, and persistent hypotension (Jarisch–Herxheimerreactions) that are associated with increases in plasma concentrationsof tumor necrosis factor (TNF-), interleukin-6, and interleukin-8.We attempted to determine whether sheep polyclonal Fab antibodyfragments against TNF- (anti–TNF- Fab) could suppressthe Jarisch–Herxheimer reaction.
Methods We conducted a randomized, double-blind, placebo-controlledtrial in 49 patients with proven louse-borne relapsing fever.Immediately before the intramuscular injection of penicillin,the patients received an intravenous infusion of either anti–TNF-Fab or a control solution.
Results Ten of the 20 patients given anti–TNF- Fab hadJarisch–Herxheimer reactions with rigors, as comparedwith 26 of the 29 control patients (P = 0.006). The controlshad significantly greater mean maximal increases in temperature(1.5 vs. 0.8°C, P<0.001), pulse rate (31 vs. 13 per minute,P<0.001), and systolic blood pressure (25 vs. 15 mm Hg, P<0.003),as well as higher mean peak plasma concentrations of interleukin-6(50 vs. 17 µg per liter) and interleukin-8 (2000 vs. 205ng per liter) (P<0.001 for both comparisons). Levels of TNF- were undetectable after treatment with anti–TNF- Fab.
Conclusions Pretreatment with sheep anti–TNF- Fab suppressesJarisch–Herxheimer reactions that occur after penicillintreatment for louse-borne relapsing fever, reduces the associatedincreases in plasma concentrations of interleukin-6 and interleukin-8,and may be useful in other forms of sepsis.
Source Information
From the Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (K.K., D.G.L., D.A.W.); the Infectious Diseases Unit, Department of Internal Medicine, Black Lion Hospital, Addis Ababa, Ethiopia (D.F., K.H., A.M.); and the Department of Chemical Pathology, Medical College of Saint Bartholomew's Hospital, London (R.E.C.).
Address reprint requests to Dr. Warrell at the Centre for Tropical Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
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