Strong association of interleukin-6 and lipopolysaccharide-binding protein with severity of adverse reactions after diethylcarbamazine treatment of microfilaremic patients.

To assess the involvement of inflammatory mediators in the development of adverse reactions in filarial patients undergoing treatment, 29 microfilaremic subjects were treated with diethylcarbamazine (DEC). Before and at serial time points after initiation of treatment, plasma levels of inflammatory mediators and DEC were measured, and adverse reactions were recorded. Patients experienced no or mild, moderate, or severe adverse reactions. Increasing pretreatment microfilarial counts were associated with escalating severity of adverse reactions. Plasma concentrations of DEC were not different among patients suffering from varying degrees of illness. Interleukin (IL)-6, IL-10, lipopolysaccharide-binding protein (LBP), and soluble tumor necrosis factor receptors (sTNF-Rs) increased after treatment. IL-6 and LBP, however, showed the strongest association with adverse reactions. Increasing levels of these molecules were closely correlated with the mounting severity of adverse reactions, which raises the possibility that they play an important role in systemic inflammation that arises after DEC treatment of filarial patients.

Adverse reactions following diethylcarbamazine (DEC) intake in 'endemic normals', microfilaraemics and elephantiasis patients.

This paper reports on adverse reactions following a 12-day course of 6 mg/kg diethylcarbamazine (DEC) therapy in brugian filariasis patients in Indonesia. Microfilaria-positive individuals (n = 26), 'endemic normals' (n = 12) and elephantiasis patients (n = 17) were included in the study. Fever, headache and body aches started between 2 and 24 h after DEC intake. Adverse reactions were categorized into 'no or mild', 'moderate' or 'severe' depending on the total reaction score. Four microfilaraemic individuals (15.4%) suffered from severe adverse reactions and their pre-treatment microfilarial levels (geometric mean, GM = 3060 mf/10 mL) were significantly higher than in the 5 microfilaraemic individuals (19.2%) suffering from moderate reactions (GM = 1268 mf/10 mL) and in the 17 microfilaraemic patients (65.4%) who experienced no or mild reactions (GM = 6 mf/10 mL)(P < 0.001 and P < 0.001, respectively). Endemic normals showed no or mild adverse reactions. No or mild adverse reactions were also recorded in all but 2 elephantiasis patients after DEC intake. Two elephantiasis patients with moderate reactions had high levels of circulating microfilariae at pre-treatment (2097 and 7375 mf/10 mL). Concentrations of DEC were measured in plasma, but could not explain the differences in the severity of adverse reactions.

Inflammatory cytokines following diethylcarbamazine (DEC) treatment of different clinical groups in lymphatic filariasis.

In an earlier study in Indonesia we reported on adverse reactions to diethylcarbamazine (DEC) in brugian filariasis patients identified as microfilaraemics (n = 26), endemic normals (n = 11) and elephantiasis patients (n = 17). To assess the link between adverse reactions and cytokines we have now analysed an array of inflammatory mediators in plasma samples collected during the same study. Pre-treatment levels of interleukin (IL)-6 and soluble tumour necrosis factor receptor 75 (sTNF-R75) were higher in elephantiasis patients compared to microfilaraemics and endemic normals, indicating the presence of an ongoing inflammation in patients with chronic disease. After initiation of treatment, the levels of IL-6 and LPS-binding protein (LBP) were consistently and significantly higher in microfilaraemics who suffered most from adverse reactions compared with endemic normals and elephantiasis patients. In microfilaraemics the levels of sTNF-R75 increased after treatment to reach levels recorded in elephantiasis patients. IL-6 increased early, concurrent with the development of adverse reactions and peaked by 24 h post treatment. The levels of LBP and sTNF-R75 in microfilaraemics also increased to peak, later than IL-6, at 32 h post DEC therapy. Although changes were recorded in IL-8 and IL-10 levels in some individuals, no significant differences were found between the 3 clinical groups. These results demonstrate that intake of DEC leads to an increase in a selected number of inflammatory mediators in the group of filarial patients who suffer most from adverse systemic reactions.