|Title:||Thl and Th2 Cytokine Profiles in Uncomplicated Measles Infection among a Group of Ghanain Children|
University of Ghana, College of Health Sciences, School of Biomedical and Allied Health Sciences, Department of Chemical Pathology
|Publisher:||University of Ghana|
|Abstract:||Measles remains a major severe infectious disease causing deaths of many children in most countries including Ghana. The disorder is associated with prolonged immunosuppression resulting in complications and mortality in children. Although attempts have been made to identify the specific immune functions altered during measles, the exact immune changes have not been fully characterized. The pro and anti-inflammatory response balances (Thl/Th2) are important in determining the pathogenesis and course of viral infections in general. CD4 mediated T cell responses to infectious agents may be dominated by type 1 or type 2 cells. Cell types are identified by the arrays of cytokine produced by each and have been clearly defined for mouse T cell clones. Similar distinctive patterns of cytokine production have been described for human T cell clones. Type 1 CD4 T cells secrete IL-2, IFN-γ and preferentially induce macrophage activation and delayed type hypersensitivity. Type 2 CD4 T cells produce IL-4, IL-5, IL-6 and IL-10, provide help for B cell responses and decrease macrophage activation. These subtypes of CD4 T cells are cross-regulatory. IFN-γ inhibits proliferation of type 2 CD4 cells whereas IL- 4 and EL-10 inhibit cytokine production by type 1 CD4 cells either directly or through their effects on macrophages. In this study, the profiles of Thl (IFN-γ, TNF-a) and Th2 (IL-4, IL-10, TGF|3) cytokine expression in vivo during uncomplicated measles among a group of Ghanaian children aged 12 years and below, mean age 6.2 ± 3.5 years were determined on days 0 (acute phase), 14 and 60 (convalescence stages). Results obtained were compared with age and sex-matched healthy controls. The results clearly showed high plasma levels of interleukin-4 (IL-4) a Th2 and an anti-inflammatory cytokine, early in the acute phase (day 0) of the disease, which declined by day 14, and day 60 post infection. Accompanying IL-4 up-regulation, Transforming growth factor β-1 (TGF-β) another anti-inflammatory cytokine also increased significantly and remained elevated in plasma samples of all patients throughout the study period (day 0, 14 and 60). The data however showed low levels of tumour necrosis factor alpha (TNF-α), a proinflammatory cytokine in the plasma samples of the patients at the acute and convalescent phases of the illness, and there was no significant difference observed between measles patients and healthy controls. Plasma levels of interleukin 12 (IL-12) and interleukin-2 (IL-2) were low in the study subjects on days 0, 14 and 60. IL-12 is critical for the orchestration of cellular immunity for the resolution of measles infection and in this study; IL-12 suppression was prolonged for 2 months after recovery from measles. Plasma levels of the Thl cytokine, interferon gamma (INF-γ) increased significantly (p<0.03) at the acute phase when compared with levels for the healthy controls. However, this increase was not maintained on days 14 and 60. Statistically significant reduction (p<0.05) in IL-10 levels was seen in days 14 and 60 samples of measles patients when compared with levels in plasma samples of healthy control group. Taken together, these data provide evidence of down-regulation of pro-inflammatory cytokine, TNF-α, and up-regulation of IL-4 an anti-inflammatory cytokine during measles infection. The mechanism by which type 2 CD4 T cells are preferentially activated during measles infection is not clear. Suggested contributing factors include genetic characteristics of the host, antigenic make-up of the pathogen, antigen dose and characteristics of the antigen presenting cell and its ability to signal T cells. The ability of measles virus to replicate in macrophages and to increase macrophage production of interleukin-1, could play a role in the preferential activation of type 1 CD4 cells that occurs during measles. This trend constitutes suppression of the immune system resulting in increased susceptibility of children to intracellular organisms and this could help to explain the many opportunistic infections associated with acute measles in Ghanaian children.|
|Appears in Collections:||Department of Chemical Pathology|
|Michael Mark Addae_ Th1 And Th2 Cytokine Profiles In Uncomplicated Measles Infection Among A Group Of Ghanaian Children_2001.pdf||Thesis (MPhil)||2.44 MB||Adobe PDF||View/Open|
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