House dust mite immunotherapy results in a decrease in Der p 2-specific IFN-gamma and IL-4 expression by circulating T lymphocytes.

Abstract

BACKGROUND: Allergen-specific immunotherapy (IT) can be an important adjunctive therapy in the treatment of allergic disorders. Although it has now been used for over 80 yr, the precise mechanism of action remains unclear. Recently a number of studies have shown that cytokine production may be modified by IT, but different protocols have been used and different results obtained. OBJECTIVES: The aims of the present study were: (1) to document the allergen-specific expression of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) by peripheral blood cells in both untreated house dust mite (HDM) allergic patients (non-IT) and following at least 10 months of HDM-specific IT (post-IT); and (2) to determine whether alterations in these critical regulatory cytokines correlated with the clinical outcome of IT. METHODS: IT was undertaken with nine fortnightly subcutaneous injections of increasing amounts of a Dermatophagoides pteronyssinus (Dpt) extract, reaching a final dose of 10,000 PNU. This was followed by 6- to 8-monthly maintenance injections of 5000 PNU. For cytokine measurement, mononuclear cells were separated from peripheral blood and stimulated with the major Dpt allergen, Der p 2, for 18 h, after which mRNA was isolated and IL-4 and IFN-gamma cDNA were amplified by polymerase chain reaction (PCR). The presence of the particular cytokine was determined by visualization following electrophoresis on an agarose gel. The study was observational in nature being open and without a placebo group. RESULTS: Fifteen Dpt-sensitive patients who had not received HDM IT (non-IT), and 16 who had, were studied. In the non-IT group, 80% expressed IL-4 and 75% expressed IFN-gamma. In those post-IT, only 12.5% expressed IL-4 and 19% IFN-gamma. The two patients still expressing IL-4 post-IT had had very little clinical response. Six patients were studied both pre- and post-IT. Prior to IT, three were positive for both cytokines, two positive for IL-4 alone and one for IFN-gamma. Post-IT, all six were negative for IL-4 and five were negative for IFN-gamma. CONCLUSION: Allergen-specific IT results in a reduction in expression of the critical cytokines IL-4 and IFN-gamma in circulating lymphocytes. It is possible that this is a contributary mechanism in the beneficial effect of IT.