Levels of gamma interferon and interleukin-4 are inversely related to the levels of their corresponding autoantibodies in patients with lower respiratory tract infection

Abstract

To study the involvement of cytokines and their corresponding autoantibodies (Aabs) in inflammatory mechanisms in patients with lower respiratory tract infections, blood samples were taken from patients at the time of admission to the hospital and before treatment. Cell-released capturing enzyme-linked immunosorbent assay was used to measure the levels of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) produced spontaneously by peripheral mononuclear cells (PMNC). ELISA was used to measure Aabs to these cytokines in sera. The levels of both cytokines were inversely related to the levels of their corresponding Aabs. While a high level of IFN-gamma was observed together with a low level of anti-IFN-gamma Aab, decreased IL-4 levels were observed with increased levels of Aabs to IL-4. Immunoglobulins were purified, digested to obtain Fab fragments, and tested for specificity and cross-reactivity. The Aabs and their Fab fragments were tested in cytokine biological assays and showed neutralizing effects. Our data demonstrated increased levels of the proinflammatory cytokine IFN-gamma and decreased release of the anti-inflammatory cytokine IL-4 during early presentation of lower respiratory tract infection. The levels of these cytokines were inversely related to the levels of their corresponding Aabs that exhibited regulatory effects on the cytokine biological function in vitro.

FIG. 1

IFN-γ and IL-4 levels and the levels of their corresponding Aabs. The left y axis shows the IFN-γ and IL-4 levels (in units per milliliter). The right y axis shows the anti-cytokine IgG Aab levels in sera of patients with lower respiratory tract infections (for relative quantification, see Materials and Methods). The data represent whole IgG binding. All samples were assayed in triplicate, and the mean ± standard deviation for each subject was first determined. Then, the means and standard deviations for all patients were calculated and are shown in the figure.

FIG. 2

Neutralizing effects of the anti-IL-4 Aabs. The effects of different dilutions of sera pooled from patients 3 and 5 on IL-4-induced PMNC proliferation are shown. The means ± standard deviations for data obtained from seven sera examined separately are shown. The asterisks indicate statistical significance (∗∗∗, P < 0.001; ∗∗, P < 0.01; ∗, P < 0.05) from the T-cell proliferation values before and after the addition of sera. rIL-4, recombinant IL-4.