D. Fekade et al., PREVENTION OF JARISCH-HERXHEIMER REACTIONS BY TREATMENT WITH ANTIBODIES AGAINST TUMOR-NECROSIS-FACTOR-ALPHA, The New England journal of medicine, 335(5), 1996, pp. 311-315
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.