Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha.
BACKGROUND
In patients with louse-borne relapsing fever (Borrelia recurrentis infection), antimicrobial treatment is often followed by sudden fever, rigors, and persistent hypotension (Jarisch-Herxheimer reactions) that are associated with increases in plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6, and interleukin-8. We attempted to determine whether sheep polyclonal Fab antibody fragments against TNF-alpha (anti-TNF-alpha Fab) could suppress the Jarisch-Herxheimer reaction.


METHODS
We conducted a randomized, double-blind, placebo-controlled trial 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-alpha Fab or a control solution.


RESULTS
Ten of the 20 patients given anti-TNF-alpha Fab had Jarisch-Herxheimer reactions with rigors, as compared with 26 of the 29 control patients (P = 0.006). The controls had 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 higher mean peak plasma concentrations of interleukin-6 (50 vs. 17 micrograms per liter) and interleukin-8 (2000 vs 205 ng per liter) (P < 0.001 for both comparisons). Levels of TNF-alpha were undetectable after treatment with anti-TNF-alpha Fab.


CONCLUSIONS
Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.
Fekade
D
D
Department of Internal Medicine, Black Lion Hospital, Addis Ababa, Ethiopia.
Knox
K
K
Hussein
K
K
Melka
A
A
Lalloo
D G
DG
Coxon
R E
RE
Warrell
D A
DA
D000293:Adolescent; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010406:Penicillins / Q000009:adverse effects*; D012061:Relapsing Fever / Q000097:blood / Q000276:immunology / Q000628:therapy*; D012756:Sheep; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D000900:Anti-Bacterial Agents; D007140:Immunoglobulin Fab Fragments; D015850:Interleukin-6; D016209:Interleukin-8; D010406:Penicillins; D014409:Tumor Necrosis Factor-alpha