L-tryptophan contaminant 'peak E' induces the release of IL-5 and IL-10 by peripheral blood mononuclear cells from patients with functional somatic syndromes

Abstract

In 1989, the development of eosinophilia myalgia syndrome (EMS) was observed in some patients after the intake of l-tryptophan containing several contaminants, including 1,1'-ethylidenebis[l-tryptophan] ('peak E'). Since l-tryptophan has been taken particularly by individuals suffering from functional somatic syndromes (FSS), such as fibromyalgia syndrome (FMS), we put forward the hypothesis that EMS may have developed preferentially in patients with FSS as an allergic reaction towards the contaminant peak E. We therefore studied the immunological reactivity towards l-tryptophan and peak E in these individuals (n = 12) and compared these data with those obtained in 12 healthy controls and 12 patients with other chronic disorders. Peripheral blood mononuclear cells (PBMC) were cultured for 7 days with pure l-tryptophan and peak E. Supernatant fluids were collected at day 7. The type 2 cytokines IL-4, IL-5 and IL-10, and the type 1 cytokines IL-2 and IFN-gamma, were determined by a double sandwich ELISA. PBMC from seven of the 12 FSS patients, but only three of the 24 controls, produced cytokines after incubation with peak E (P < 0.05). Interestingly, six of the seven FSS patients reacting with peak E produced IL-5 and/or IL-10. In contrast, PBMC from only one patient with other chronic disorders and one healthy control secreted type 2 cytokines in response to peak E. The observed heightened type 2 reactivity towards the more immunogenic contaminant 1,1'-ethylidenebis[l-tryptophan] in FSS patients may therefore be taken as an additional argument for our concept that EMS may have developed as a kind of drug-induced allergic disease.

Fig. 1

Cytokine production by PBMC of (a) FSS patients and (b) control individuals. Only the seven FSS patients (nos 1, 2, 3, 6, 8, 9 and 12) and three control individuals (nos 15, 17 and 21), in whom type 1/type 2 related cytokines could be demonstrated in response to peak E, are shown. Cytokines are expressed as pg/ml. (Type 1 profile: secretion of IFN-γ; type 2 profile: secretion of either IL-5 or IL-10; type 0 profile: secretion of IFN-γ and IL-5/IL-10 in parallel). One FSS patient produced only IFN-γ (no. 8), four only IL-5 (nos 3 and 12) or IL-10 (nos 1 and 6) and two IFN-γ and IL-5 or IL-10 in parallel (nos 2 and 9). Of the controls, one produced only IFN-γ (no. 17), one only IL-10 (no. 21) and one IFN-γ and IL-10 in parallel (no. 15). (+) no. 8; (▴) no. 3; (▾) no. 12; (♦) no. 1; (×) no. 6; (▪) no. 2; (•) no. 9; (▿) no. 17; (□) no. 21; (▵) no. 15. (Dotted line: IL-10; continuous line: IL-5).