LEVELS OF CYTOKINES AND IMMUNE ACTIVATION MARKERS IN PLASMA IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - QUALITY-CONTROL PROCEDURES

Procedures for quality control (QC) in a laboratory that concentrates on cytokine and soluble marker measurements in biological fluids are o utlined. Intra-assay, interassay, and interlaboratory experiences are presented. Plasma and serum beta 2-microglobulin (beta 2M) and neopter in test data are presented in greatest detail, along with substantial tumor necrosis factor alpha (TNF-alpha), gamma interferon, soluble int erleukin-2 receptor-alpha (sIL-2R alpha), sTNF-RII, IL-4, and IL-6 dat a. Recommended QC procedures for cytokine and soluble-marker testing i nclude replicate testing of two or more reference samples provided by the kit manufacturer, replicate testing of in-house frozen reference Q C samples that represent normal and abnormal analyte contents, retesti ng 15 to 20% of randomly selected samples, and comparing normal refere nce ranges each year. Also, eight cytokines and soluble markers were e valuated in human immunodeficiency virus (HIV)-seronegative and HIV-se ropositive individuals stratified on the basis of CD4 T-cell numbers. Levels of some but not all cytokines in serum increased in HIV infecti on. There was a tendency for cytokines to increase with more advanced disease, defined by reduced CD4 T-cell numbers. Cytokine changes did n ot relate closely to CD4 level, indicating that separate information w as provided by the measurements of TNF-alpha, sTNF-RII, sIL-2R alpha, beta 2M, and neopterin. Serum IL-4 and TNF-alpha levels were not incre ased. The quality of laboratory data can impact on clinical relevance. Interlaboratory comparisons revealed substantial differences at some sites and documented the need for external proficiency-testing quality assurance programs.