Serum Interleukin-6 Levels and Pulmonary Function in Ataxia-Telangiectasia.

OBJECTIVE: To evaluate the potential link between systemic inflammation and impaired lung function in people with ataxia-telangiectasia (A-T), we hypothesized that serum levels of interleukin (IL)-6, a proinflammatory cytokine, would correlate inversely with lung function in subjects with A-T. STUDY DESIGN: Consecutive subjects with A-T were recruited from the Johns Hopkins Outpatient A-T Clinical Center. Serum levels of IL-6 and 8 were measured by enzyme-linked immunosorbent assay. Spirometry was performed in subjects ≥ 6 years of age on the same day that serum was obtained for measurements of cytokines. RESULTS: Approximately 80% of subjects had elevated serum IL-6 levels (> 1.0 pg/mL). No association was found between elevated IL-6 and age. Elevated IL-8 levels were found in 23.6% of subjects, and all subjects with elevated IL-8 levels had elevated IL-6 levels. Subjects with elevated IL-6 levels (mean: 6.14 ± 7.47 pg/mL) had significantly lower mean percent forced vital capacity (FVC%, 50.5% ± 17.8%) compared with subjects with normal serum IL-6 levels (FVC% of 66.2 ± 16.1, P = .018). Greater IL-6 levels were associated with lower FVC% even after adjustment for receiving gamma globulin therapy (P = .024) and supplemental nutrition (P = .055). CONCLUSIONS: An association was found between elevated serum IL-6 levels and lower lung function in subjects with A-T. In addition, subjects with both elevated IL-6 and IL-8 had the lowest mean lung function. These findings indicate that markers for systemic inflammation may be useful in identifying individuals with A-T at increased risk for lower lung function and may help in assessing response to therapy.

Elevated serum IL-8 levels in ataxia telangiectasia.

Serum interleukin (IL)-8 levels were measured in 50 patients with ataxia telangiectasia (A-T) and 22 without A-T. In a cross-sectional study, the geometric mean of IL-8 level was significantly higher in the patients with A-T (P <.0001). Elevated serum IL-8 levels in patients with A-T suggest that systemic inflammation may contribute to the disease phenotype.

Immunodeficiency and infections in ataxia-telangiectasia.

OBJECTIVE: To characterize the immunodeficiency in ataxia-telangiectasia (A-T) and to determine whether the immunodeficiency is progressive and associated with increased susceptibility to infections. STUDY DESIGN: Records of 100 consecutive patients with A-T from the Johns Hopkins Ataxia-Telangiectasia Clinical Center (ATCC) were reviewed. RESULTS: Immunoglobulin (Ig) deficiencies are common, affecting IgG4 in 65% of patients, IgA in 63%, IgG2 in 48%, IgE in 23%, and IgG in 18%. Lymphopenia affected 71% of patients, with reduced B-lymphocyte number in 75%, CD4 T lymphocytes in 69%, and CD8 T lymphocytes in 51%. There was no trend for increased frequency or severity of immune abnormalities with age. Recurrent upper and lower respiratory tract infections were frequent: otitis media in 46% of patients, sinusitis in 27%, bronchitis in 19%, and pneumonia in 15%. Sepsis occurred in 5 patients, in 2 patients concurrent with cancer chemotherapy. Warts affected 17% of patients, herpes simplex 8%, molluscum contagiosum 5%, candidal esophagitis 3%, and herpes zoster 2%. Uncomplicated varicella infection occurred in 44% of patients; 2 patients had more than one clinical episode. No patient had Pneumocystis jerovici pneumonia or a complication of live viral vaccine. CONCLUSIONS: In spite of the high prevalence of laboratory immunologic abnormalities, systemic bacterial, severe viral, and opportunistic infections are uncommon in A-T. Cross-sectional analysis suggests that the immune defect is rarely progressive.

Cryptosporidiosis stimulates an inflammatory intestinal response in malnourished Haitian children.

The mechanisms by which Cryptosporidium parvum cause persistent diarrhea and increased morbidity and mortality are poorly understood. Three groups of Haitian children <18 months old were studied: case patients, children with diarrhea not due to Cryptosporidium, and healthy control subjects. Compared with both control groups, children with acute cryptosporidiosis were more malnourished (including measures of stunting [P=.03] and general malnutrition [P=.01]), vitamin A deficient (P=.04), and less often breast-fed (P=.04). Markers of a proinflammatory immune response, interleukin (IL)-8 and tumor necrosis factor-alpha receptor I, were significantly elevated in the case population (P=.02 and P<.01, respectively), as was fecal lactoferrin (P=.01) and the T helper (Th)-2 cytokine IL-13 (P=.03). The counterregulatory cytokine IL-10 was exclusively elevated in the case population (P<.01). A Th1 cytokine response to infection was not detected. This triple cohort study demonstrates that malnourished children with acute cryptosporidiosis mount inflammatory, Th-2, and counterregulatory intestinal immune responses.