Levels of Interleukin-2, Interferon-g, and Interleukin-4 in Bronchoalveolar Lavage Fluid From Patients With Mycoplasma Pneumonia: Implication of Tendency Toward Increased Immunoglobulin E Production

Objective. In connection with the possible relationship between Mycoplasma infection and the onset of asthma, several studies have shown not only a high level of serum total immunoglobulin E (IgE) but also the production of IgE specific to Mycoplasma or common allergens during the course of Mycoplasma infection. It has been suggested that the balance of T helper type 1 (TH1)/T helper type 2 (TH2) immune response may regulate the synthesis of IgE. The objective of this study was to investigate the pattern of cytokine response (TH1 or TH2) during an episode of acute lower respiratory tract infection caused by Mycoplasma pneumoniae. Study Design. Using a bronchoalveolar lavage (BAL) with flexible bronchoscopy procedure, this study determined the levels of interleukin (IL)-2, interferon (IFN)-g (TH1), and IL-4 (TH2) in the supernatant of BAL fluid as well as the BAL cellular profiles of patients with Mycoplasma pneumonia (n 5 14). These results were compared with those of patients with pneumococcal pneumonia (n 5 12) or those of children with no identifiable airway infections (control group: n 5 8). Results. The BAL cellular profile in the Mycoplasma pneumonia group was characterized by a high percentage of neutrophils and lymphocytes. A significantly increased level of IL-2 was found in both pneumonia groups, compared with the control group. In contrast, the IFN-g level was not different for the 3 groups. The level of IL-4 and ratio of IL-4/IFN-g were significantly elevated in the Mycoplasma pneumonia group, but not in the pneumococcal pneumonia group, compared with the controls. Conclusions. IL-4 levels and IL-4/IFN-g ratios in BAL fluid are significantly higher in patients with Mycoplasma pneumonia than in patients with pneumococcal pneumonia or control participants. The BAL cytokine data suggest a predominant TH2-like cytokine response in Mycoplasma pneumonia, thus representing a favorable condition for IgE production. Pediatrics 2001;107(3). URL: http://www.pediatrics.org/cgi/content/full/107/3/ e39; interleukin-2, interferon-g, interleukin-4, bronchoalveolar lavage, Mycoplasma, pneumococcus, pneumonia. ABBREVIATIONS. IgE, immunoglobulin E; TH1, T helper type 1; TH2, T helper type 2; IFN, interferon; IL, interleukin; BAL, bronchoalveolar lavage; FB, fiber-optic bronchoscopy; SD, standard deviation. Results of several studies over the past decade have provided evidence linking Mycoplasma infection with asthma exacerbation and have raised the possibility that Mycoplasma infection is a factor in the pathogenesis of asthma. An acute exacerbation of wheezing in asthmatic participants in association with Mycoplasma infection has been welldocumented.1,2 In addition, Mycoplasma pneumoniae has been found in the lower airways of chronic, stable asthmatics with a greater frequency than in control participants,3 suggesting a pathogenic mechanism in chronic asthma. It has even been suggested that Mycoplasma infection may be responsible for the subsequent development of asthma. In a follow-up study of 50 children with Mycoplasma respiratory illness, 5 developed clinical signs of asthma for the first time.4 There is also a report that describes a previously healthy participant who had an initial asthmatic attack after recovering from Mycoplasma pneumonia.5 Several studies support the theory of a possible relationship between Mycoplasma infection and the onset of asthma. It has been reported that Mycoplasma infections could induce transient or persistent airway hyperresponsiveness.5–7 The level of serum total immunoglobulin E (IgE) has been shown to increase in the acute phase of Mycoplasma infection.8 As has been reported for virus infection, wheezing during Mycoplasma infection may be related to higher serum IgE levels.9 Mycoplasma-specific IgE10 and IgE specific to common allergens unrelated to the infectious agent8 have been detected during the course of Mycoplasma infection. Although the baseline IgE levels have not been presented to be certain that the increase in IgE is caused by Mycoplasma infections, these observations raise the possibility that Mycoplasma infections may stimulate an inflammatory response that promotes IgE production. The development of cellular or humoral immune responses will depend on a repertoire of cytokines produced by numerous cells, including CD41 helper T cells. These lymphocytes can be subdivided into 2 subsets, T helper type 1 (TH1) and T helper type 2 From the *Department of Pediatrics and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; and the ‡Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea. Received for publication Jul 5, 2000; accepted Sep 26, 2000. Reprint requests to (Y.Y.K.) Department of Pediatrics, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea. Email: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 2001 by the American Acad-