PREVENTION OF JARISCH-HERXHEIMER REACTIONS BY TREATMENT WITH ANTIBODIES AGAINST TUMOR-NECROSIS-FACTOR-ALPHA

Background In patients with louse-borne relapsing fever (Borrelia recu rrentis infection), antimicrobial treatment is often followed by sudde n fever, rigors, and persistent hypotension (Jarisch-Herxheimer reacti ons) that are associated with increases in plasma concentrations of tu mor necrosis factor alpha (TNF-alpha), interleukin-6, and interleukin- 8. We attempted to determine whether sheep polyclonal Fab antibody fra gments against TNF-alpha (anti-TNF-alpha Fab) could suppress the Jaris ch-Herxheimer reaction. Methods We conducted a randomized, double-blin d, placebo-controlled trial in 49 patients with proven louse-borne rel apsing fever. Immediately before the intramuscular injection of penici llin, the patients received an intravenous infusion of either anti-TNF -alpha Fab or a control solution. Results Ten of the 20 patients given anti-TNF-alpha Fab had Jarisch-Herxheimer reactions with rigors, as c ompared with 26 of the 29 control patients (P = 0.006). The controls h ad significantly greater mean maximal increases in temperature (1.5 vs . 0.8 degrees 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 hi gher mean peak plasma concentrations of interleukin-6 (50 vs. 17 mu g per liter) and interleukin-8 (2000 vs. 205 ng per liter) (P<0.001 for both comparisons). Levels of TNF-alpha were undetectable after treatme nt with anti-TNF-alpha Fab. Conclusions Pretreatment with sheep anti-T NF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the asso ciated increases in plasma concentrations of interleukin-6 and interle ukin-8, and may be useful in other forms of sepsis. (C) 1996, Massachu setts Medical Society.