Sequence of immunoglobulin isotype exposure modulates inflammatory response to bacteria and lipopolysaccharide in vitro.

ABSTRACT

BACKGROUND: Secretory immunoglobulin A (sIgA) and immunoglobulin G (IgG) are the principal immunoglobulins in the respiratory tract. Under normal circumstances, the upper respiratory tract contains predominantly sIgA, whereas IgG is of primary importance in the lower tract. Unlike other antibody isotypes, IgA antibodies participate in host defense functions without inciting inflammatory processes that might cause collateral damage to tissues. However, the ability of sIgA to modulate inflammatory reactions induced by other humoral factors is unclear. We examined the effect of the sequence of exposure to the two immunoglobulin isotypes on bacteria- or lipopolysaccharide (LPS)-mediated cytokine production by monocyte-polymorphonuclear neutrophil (PMN) cells in vitro. METHODS: Blood monocytes were co-cultured with Escherichia coli or LPS. Either sIgA or IgG was added to subsets of cultures, which were incubated for 1 h at 37 degrees C. Culture supernatant liquids were then co-cultured with naïve PMNs for 1 h at 37 degrees C. Either IgG was added during this co-culture step or sIgA was added if IgG was added first. Cytokines were quantitated by enzyme-linked immunosorbent assay. RESULTS: Significant increases in interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-8 were noted after E. coli or LPS co-culture with monocytes and subsequent PMN challenge. Marked decreases in these pro-inflammatory cytokines were seen after the addition of sIgA or sIgA-IgG but not after IgG alone. This effect was more apparent with the immunoglobulin sequence IgA followed by IgG. CONCLUSION: The sequence of immunoglobulin isotype involvement in infectious processes is important in modulating the cytokine response to bacteria and LPS by inflammatory cells. Our in vitro results support the critical role of sIgA in the proximal airways in mitigating inflammatory responses by other humoral defenses in the distal airways. Loss of effective sIgA function may contribute to increased morbidity and deaths from nosocomial pneumonia in compromised patients.