Interleukin (IL)-4, IL-5 and interferon (IFN)-gamma are thought to play an important role in chronic airway inflammation in asthmatic subjects. Increased airways responsiveness and nocturnal airway obstruction are important clinical manifestations of asthma. The aim of this study was to investigate whether IL-4, IL-5 and IFN-gamma values are elevated in atopic asthma and correlate with its clinical manifestations. Serum IL-4, IL-5 and IFN-gamma levels of 17 atopic asthmatics and eight nonatopic healthy subjects were determined at 16:00 and 04:00 h by a chemiluminescence enzyme-linked immunosorbent assay (ELISA) method. The clinical manifestation of asthma was determined by assessment of the degree of airway obstruction, airways responsiveness to methacholine and severity of nocturnal airway obstruction, defined as the mean circadian (16:00-04:00 h) peak expiratory flow (PEF) variation. Serum IL-4, IL-5 and IFN-gamma levels were significantly higher in asthmatic subjects as compared to healthy controls, both at 16:00 and 04:00 h. In asthmatic subjects serum IFN-gamma at both time points correlated significantly with the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20,meth) (rho= - 0.55) and with the mean 16:00-04:00 h PEF variation (rho = 0.53). In contrast, no relationship was found between the levels of IL-4 and IL-5 and the parameters of clinical manifestation of asthma. The results suggest that the serum interferon-gamma level is a reflection of the severity of airway inflammation in atopic asthma. More studies are needed to detect the cellular sources and to clarify the exact roles of interferon-gamma and other pro-inflammatory cytokines in asthma.

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Background: Five to twenty percent of healthy, nonasthmatic individuals exhibit airway hyperreactivity. Because cytokines are important intermediates in airway responses, we investigated the relationship between serum cytokines and airway responsiveness in a well-characterized population of pregnant women. Methods: We analyzed serum levels of interleukin-4 (IL-4), IL-5, IL-6, interferon-γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in frozen sera from 240 pregnant nonasthmatic subjects from a previous study of airway responsiveness and preterm labor for their relationship to methacholine challenge test results. Results: Serum IFN-γ and GM-CSF levels were significantly related to levels of methacholine airway responsiveness among nonasthmatics in this population. Nonasthmatics with PD₂₀ <8 µmol (the highest level of airway responsiveness) had the highest mean serum levels of IFN-γ and GM-CSF, those with 8 ≤ PD₂₀ ≤ 50 µmol had intermediate levels, and those with PD₂₀ >50 µmol had the lowest levels. Both serum IFN-γ and GM-CSF levels were also significantly related to the log dose-response slope for methacholine responsiveness. These relationships were confirmed in a multiple linear regression analysis controlling for age, ethnic background, and cigarette smoking. Current smoking was uniformly associated with decreased cytokine levels. Conclusion: IFN-γ, GM-CSF, and other cytokines may be useful serum markers in population studies of airway responsiveness.

Objectives: Cytokines are critical regulatory molecules that circulate in blood at measurable levels. However, the epidemiology of serum cytokine levels in healthy populations is still limited, particularly for Japanese populations. The objective of this study was to examine the relation between serum cytokine levels and common laboratory tests in a healthy Japanese population.Methods: We studied serum levels of six cytokines (interleukin-4 (IL-4), IL-5, IL-6, IL-10, interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF)) in a healthy Japanese population using a sensitive chemiluminescence ELISA (CL-ELISA). We examined the relations between serum cytokine levels and common laboratory tests using multiple regression analysis. We were particularly interested in potential relations between serum cytokine levels and C-reactive protein (CRP) in light of its relation to the risk of cardiovascular events. We also investigated the relation between cytokine levels, alcohol consumption and smoking.Results: After adjusting for the influence of other cytokines and laboratory tests, the serum level of IL-4 was associated with IL-5 and GM-CSF. In addition to IL-4, IL-5 was also associated with IL-10 and IFN-γ. IL-6 was associated with IL-10 and IFN-γ, and IL-10 and IFN-γ were associated with GM-CSF. CRP was significantly negatively associated with serum IL-4 level. IL-6 was weakly correlated with alcohol consumption level in this population. IL-5 among smokers tended to be lower than that among nonsmokers.Conclusions: Close relations among serum cytokine levels were observed in a healthy population. It is interesting that the level of IL-4, an anti-inflammatory cytokine, was inversely related to CRP level, suggested to be a marker of inflammation.

Acute pulmonary neutrophilic inflammation triggered by cotton dust exposure is one of the features of organic dust syndrome. Studies with a mouse model have reproduced the inflammation and have shown the presence of tumor necrosis factor-alpha (TNF-alpha) in the bronchoalveolar lavage (BAL) fluid of mice following a 3-h exposure to respirable cotton dust particles. A cover glass technique for cytospin samples of BAL cells resulted in a 42-fold increase in cell count, with 76% neutrophils, 13% lymphocytes, and 10% macrophages, after cotton dust exposure. Immunohistochemical staining of lung specimens with anti-TNF-alpha antiserum revealed TNF in the cells surrounding pulmonary airways and vessels. Cotton dust exposure resulted in elevated TNF-alpha, IL-6, and INF-gamma in BAL fluid, INF-gamma and IL-6 in serum. Administration of anti-TNF-alpha antiserum prior to the organic dust exposure resulted in a marked attenuation of the pulmonary inflammatory cell response, as well as decreased IL-6 and TNF-alpha levels in BAL fluid and decreased IL-6 and INF-gamma in serum. These results indicate TNF modulation of the dust-induced toxic alveolitis and cytokine production.