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

Koh, Young Yull; Park, Yang; Lee, Hoan Jong; Kim, Chang Keun

doi:10.1542/peds.107.3.e39

Cited by 79 publications

(57 citation statements)

References 31 publications

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“…These differences may explain the different results. Our total serum IgE results showed some agreement with those of other studies done after acute M. pneumoniae infection (10,13,18,19) and also revealed a marked chronicity of total serum IgE increase. (7).…”

supporting

confidence: 91%

Humoral and Cellular Immunity in Children withMycoplasma pneumoniaeInfection: a 1-Year Prospective Study

Stelmach¹,

Podsiadłowicz-Borzęcka²,

Grzelewski³

et al. 2005

Clin Vaccine Immunol

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To determine whether children have persistent abnormalities in cellular and humoral immunity development after acute Mycoplasma pneumoniae infection, serum immunoglobulin G (IgG), IgA, IgM, and IgE levels and lymphocyte phenotypes were determined. There were no changes in the levels of IgG, IgM, IgA, or CD4 ؉ or CD19؉ lymphocytes that were measured in M. pneumoniae-positive patients after 3 months or after 12 months, but there were increases in these in M. pneumoniae-negative patients. Serum IgE increased in M. pneumoniae-positive patients. We have shown alterations in immunity development after M. pneumoniae infection.Mycoplasma pneumoniae is a common pathogen of children's respiratory tracts (8), and its abilities to act as a polyclonal activator of lymphocytes and autoantibodies to various tissues and immune complexes are well known (2, 16). CD4 ϩ T cells, B cells, and plasma cells infiltrate the lungs, which is followed by further amplification of the immune response, namely, proliferation of lymphocytes, production of immunoglobulins, and release of proinflammatory cytokines (3,14). It has been previously described that the levels of total immunoglobulins, immunoglobulin A (IgA), IgM, and IgG, in serum increase during the convalescent phase of the disease (19) and that there is production of IgE specific to M. pneumoniae during infection (18). The bronchoalveolar lavage cytokine data suggest a predominant Th2-like cytokine response in M. pneumoniae infections, thus representing a favorable condition for IgE production (7), although other results suggest a Th1 cytokine response predominance (5, 21).Previous studies are confined to the acute phase of M. pneumoniae infection and do not answer questions about the possible duration of the humoral and cellular imbalance after M. pneumoniae infection in children. In this study, we hypothesized that children may have persistent abnormalities in cellular and humoral immunity development after acute M. pneumoniae infection.The study participants included 110 patients (52 male and 58 female) aged 1 to 5 years, all suffering from recurrent respiratory tract infections, defined according to Ribeiro (15). The diagnosis of M. pneumoniae infection was based on clinical symptoms (12,20) and the presence of IgM, determined by enzyme-linked immunosorbent assay (ELISA) and confirmed by PCR. Children diagnosed with M. pneumoniae infection were treated with clarithromycin (4). None of the patients had previously suffered from allergic disease or immunodeficiency syndrome. The characteristics of the patients are presented in Table 1.There were five study visits. At the first visit, patients were informed about the purpose of the study and were told that the second visit would occur after 3 months or earlier (in the case of respiratory tract infection). The patient's medical history was recorded, a physical examination was done, and blood samples for IgG, IgA, IgM, and IgE serum levels and lymphocyte phenotypes were taken at each visit. During the second visit, a blood sample was ...

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supporting

confidence: 91%

Humoral and Cellular Immunity in Children withMycoplasma pneumoniaeInfection: a 1-Year Prospective Study

Stelmach¹,

Podsiadłowicz-Borzęcka²,

Grzelewski³

et al. 2005

Clin Vaccine Immunol

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“…Our data are consistent with earlier reports that a high percentage of neutrophils are present in BALF of patients with M. pneumoniae and that the levels of various cytokines are elevated in BALF (17,23,33,50). These findings suggest that lipoproteins of M. pneumoniae contribute to the pathogenesis of M. pneumoniae infection.…”

Section: Discussionsupporting

confidence: 93%

Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice

2008

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The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F 0 F 1 -type ATPase (F 0 F 1 -ATPase), NF-B-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived from M. pneumoniae induce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-␣) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-␣ in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived from Mycoplasma fermentans and Mycoplasma salivarium, respectively. These findings indicate that the F 0 F 1 -ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses during M. pneumoniae infection in vivo.Mycoplasmas are wall-less parasitic bacteria and the smallest organisms capable of self-replication (48). Mycoplasma pneumoniae causes primary atypical pneumonia, tracheobronchitis, pharyngitis, and asthma in humans (7,19,20). However, pathogenic agents such as endotoxin and exotoxin that cause such diseases have not been identified in M. pneumoniae. Adherence of invading mycoplasmas to the respiratory epithelium, localized host cell injury, and an overaggressive inappropriate immune response seem to contribute to the pathogenesis of M. pneumoniae infection (46).Recently, it has been reported that Toll-like receptors (TLRs) with the function of pattern recognition receptors play critical roles in early innate recognition and inflammatory responses of the host against invading microbes (1, 18). Among 10 TLR family members reported, TLR2, TLR4, TLR5, and TLR9 have been implicated in the recognition of different bacterial components. Peptidoglycan, lipoarabinomannan, zymosan, and lipoproteins from various microorganisms are recognized by TLR2 (2,3,24,26,43,44,47). On the other hand, lipopolysaccharide (LPS), bacterial flagellin, and bacterial DNA are recognized by TLR4, TLR5, and TLR9, respectively (9, 10, 13, 34). These TLR family members have been shown to activate nuclear factor B (NF-B) via interleukin-1 (IL-1) receptor-associated signal molecules, including myeloid differentiation protein (MyD88), IL-1 receptor-activated kinase, tumor necrosis factor (TNF) receptor-associated factor 6, and NF-B-inducing kinase (27).We previously demonstrated that lipid-associated membrane proteins from M. pneumoniae can induce NF-B activation, and we subsequently identified three lipoproteins responsible for NF-B activation. One was MPN602, known as s...

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“…Further amplification of the immune response in association with lymphocyte proliferation, production of immunoglobulins, and release of tumor necrosis factor alpha (TNF-␣), gamma interferon (IFN-␥), and various interleukins (including interleukin-1␤ [IL-1␤], IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-18) occurs, based on evidence from clinical and in vitro studies and from animal models (193,195,263,308,309,406,420,447,448). Many of these reactive substances will have elevated levels in both alveolar fluid and serum (233,263,406,448). Yang et al (448) recently reported that M. pneumoniae infection of human epithelial carcinoma cells in vitro resulted in increased levels of IL-8 and TNF-␣ mRNAs and that both proteins were secreted into culture medium.…”

Section: Cytotoxicity and Inflammationmentioning

confidence: 99%

Mycoplasma pneumoniaeand Its Role as a Human Pathogen

2004

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Mycoplasma pneumoniae is a unique bacterium that does not always receive the attention it merits considering the number of illnesses it causes and the degree of morbidity associated with it in both children and adults. Serious infections requiring hospitalization, while rare, occur in both adults and children and may involve multiple organ systems. The severity of disease appears to be related to the degree to which the host immune response reacts to the infection. Extrapulmonary complications involving all of the major organ systems can occur in association with M. pneumoniae infection as a result of direct invasion and/or autoimmune response. The extrapulmonary manifestations are sometimes of greater severity and clinical importance than the primary respiratory infection. Evidence for this organism's contributory role in chronic lung conditions such as asthma is accumulating. Effective management of M. pneumoniae infections can usually be achieved with macrolides, tetracyclines, or fluoroquinolones. As more is learned about the pathogenesis and immune response elicited by M. pneumoniae, improvement in methods for diagnosis and prevention of disease due to this organism may occur

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Levels of Interleukin-2, Interferon-γ, and Interleukin-4 in Bronchoalveolar Lavage Fluid From Patients WithMycoplasmaPneumonia: Implication of Tendency Toward Increased Immunoglobulin E Production

Cited by 79 publications

References 31 publications

Humoral and Cellular Immunity in Children withMycoplasma pneumoniaeInfection: a 1-Year Prospective Study

Humoral and Cellular Immunity in Children withMycoplasma pneumoniaeInfection: a 1-Year Prospective Study

Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice

Mycoplasma pneumoniaeand Its Role as a Human Pathogen

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