The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever

Abstract

Severe Jarisch Herxheimer reaction (J-HR) precipitated by antibiotic treatment of louse-borne relapsing fever (LBRF) is associated with a transient, marked rise in circulating tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). Ovine polyclonal anti-TNF alpha antibody fragments (Fab) were used in a randomized double blind placebo controlled trial in an attempt to prevent this reaction. Within 4 h after penicillin, in controls (n = 29), a several-fold rise in cytokines occurred, concomitant with a fall in spirochaetes and maximal clinical manifestations of the J-HR. An intravenous infusion of anti-TNF alpha Fab, 30 min before penicillin in 20 patients reduced peak plasma levels of IL-6 and IL-8 (but not IL-1 beta) compared with controls (p = 0.01 and < 0.001, respectively) and the incidence of the J-HR, indicating some neutralization of TNF alpha. An apparent fall in TNF alpha reflected interference of anti-TNF alpha in the immunoassay.

Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria.

“…For example, there was a large difference in FCTs reported in two large recent studies in Vietnam and in The Gambia that used artemether (with median values of 127 and 30 hr, respectively). 11,14 A further important endpoint used in malaria studies is mortality, but this is so low in the unit where this study was conducted (4% in the present study) that a very large study would be required. However, the time course for clinical improvement was encouragingly short and is reassuring that the antibody is not prolonging the natural history of the infection.…”

“…The TNF-␣ and IL-6 values on admission were similar to those found in patients with louse-borne relapsing fever (LBRF) before treatment. 11 However, whereas antibiotic treatment of LBRF induces an explosive release of these cytokines, artesunate treatment did not. In the control group, concentrations of most cytokines remained consistently very high or gradually decreased over the following 2-day period.…”

“…Previous studies have shown that the Fab bound to TNF-␣ is no longer recognized by the immunoassay. 11 Most patients had mildly elevated IFN-␥ concentrations on admission, although one patient had a very high concentration (310 IU/ml). After treatment, concentrations of IFN-␥ gradually decreased for 48 hr, but two patients had a transient reoccurrence.…”

“…The reduction seen in TNF-␣ levels after antibody treatment is, at least in part, due to the Fab binding the TNF-␣ so that the resulting complex can no longer be bound by the antibodies used in the immunoassay. 11 To detect significant reductions in IFN-␥ and IL-6 concentrations would require a larger study.…”

Relapsing Fever Borreliae in Africa

“…28,29 This reaction is associated with the release of cytokines during the clearance of borreliae from the blood. 30 A few studies indicated that the administration of antibodies against tumor necrosis factor-alpha does prevent Jarisch-Herxheimer reaction during relapsing fever, 31,32 however such expensive medications are not currently available in African countries where relapsing fevers are endemic. Because field experience in Africa has indicated that relapsing fevers are readily cured by antibiotics, there has been no need for the in vitro susceptibility testing of antibiotics.…”