• Augusto A Litonjua, David Sparrow, Lucille Guevarra, George T O'Connor, Scott T Weiss, and David J Tollerud.
• Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. augusto.litonjua@channing.harvard.edu
• Ann. Allergy Asthma Immunol. 2003 Apr 1;90(4):422-8.

BackgroundCytokines are important mediators of the asthmatic response. A retrospective pilot study showed that serum levels of interleukin (IL)-5 and interferon (IFN)-gamma were related to lung function decline among asthmatic patients over the preceding 3 years. To confirm these findings, we tested the hypothesis that serum cytokines are associated with longitudinal lung function decline.MethodsWe conducted a prospective, longitudinal study of 25 asthmatic and 50 nonasthmatic men (median age, 63 years; range, 45 to 80 years) participating in the Normative Aging Study. All study subjects completed two consecutive triennial examinations, including spirometry, methacholine challenge testing, allergy skin testing, and phlebotomy. Serum levels were measured for IL-4, IL-5, IL-6, IL-8, IL-10, and IFN-gamma.ResultsAmong asthmatic patients, a higher initial serum level of IFN-gamma was associated with a greater rate of decline of forced expiratory volume in 1 second (FEV1; beta = -67 mL/year per log increase in serum IFN-gamma, P = 0.04) and, to a lesser extent, of FEV1/forced vital capacity ratio (beta = -0.91%/year per log increase in serum IFN-gamma, P = 0.07) after adjusting for age, smoking status, and baseline level of lung function. Serum IL-5 level was associated with a rate of decline in FEV1 of borderline significance (beta = -61 mL/year per log increase in serum IL-5, P = 0.08) among asthmatic patients. These relationshipswere not observed among nonasthmatic patients.ConclusionsSerum levels of IFN-gamma are associated with subsequent rate of change in lung function among asthmatic patients in this cohort of middle-aged and older men, and may be useful as biologic markers of risk for accelerated lung function decline in population studies.

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