The Expression Of TNF-α, IFN-γ, TGF-β And IL-10 In Spinal Tuberculous Lesions And The Influence Of Them On The Severity Of Local Pathological Changes

Objective:Up to now,relatively little is known about the mechanisms by which the human immune system influences Mycobacterium tuberculosis infection in spinal vertebrae.This study was to investigate the expression of tumour necrosis factor-α(TNF-α),interferon-γ(IFN-γ),transforming growth factor-β(TGF-β) and interleukin-10(IL-10) in human spinal tuberculous lesions and to elaborate on the role of them in the appearance of vertebral bony destruction using immunohistochemistry.Methods:From Jan 2007 to November 2008,a total of 30 patients with spinal tuberculosis were included in this study.The research was performed on spinal tuberculous vertebral bony biopsies taking in the operation in our hospital.All patients presented with symptoms of spinal tuberculosis and had radiological and pathological or bacterial confirmation of the desease.The patients were in the active stage of the disease,they were divided into hyperplastic and caseous necrotic type according to the radiological character and observation in the operation.There were 12 patients in the group of hyperplastic type and 18 in the group of caseous necrotic type.Control vertebral bony biopsies were obtained from ten randomly chosen individuals who had vertebral body resection for localized conditions other than spinal tuberculosis.Control vertebral body tissues were histologically normal.The sections were stained with HE and TRAP stain, immunohistochemistry was performed for TNF-α,IFN-γ,TGF-β,and IL-10, two-dimensional morphometric analyses were performed for the the expression of the cytokines in tuberculous granulomas,the same method of analysis was performed on the bony destruction area.Positive staining areas were identified by microscopy and captured as a digitial picture,the mean percent of positive staining area to the total microscopic area was calculated using the Image Pro Plus software.Statistical analysis were performed to compared between the patients and control groups.Differences were considered significant when p values were less than 0.05.Results:1.Based on HE and TRAP stain,the percent of necrotic granulomas in the group of caseous necrotic type were higher than that in the group of hyperplastic type(p＜0.01).The cells in hyperplastic and caseous necrotic type expressed cytokines differently.The expression of TNF-αand IFN-γin granulomas of hyperplastic type group were higher than that in granulomas of caseous necrotic type group(p＜0.01).The expression of TGF-βand IL-10 in granulomas of caseous necrotic type were higher than that in hyperplastic type (p＜0.01).The expression of IFN-γin necrotic granulomas of hyperplastic type were lower than that in non-necrotic granulomas of the same type(p＜0.05).The expression of TGF-βin necrotic granulomas of caseous necrotic type were higher than that in non-necrotic granulomas of the same type(p＜0.01).The expression of TNF-αin necrotic granulomas of caseous necrotic type were lower than that in non-necrotic granulomas of the same type(p＜0.01).The expression of TNF-α, IFN-γ,TGF-βand IL-10 were correlated positively with each other in granulomas of hyperplastic type group.The expression of TNF-αwere correlated negatively with the expression of TGF-βin necrotic granulomas of caseous necrotic type group.2.The representation of bony destruction in the group of hyperplastic type was characterized as bony resorption.The feature of bony destruction in the group of caseous necrotic type was bony necrosis associated with the medullary fibrosis and bony forming.The local expression of TNF-αand IFN-γwere correlated positively with the degree of bony resorption in the group of hyperplastic type.The expression of TGF-βand IL-10 were correlated positively with the local bony forming in the group of caseous necrotic type.Conclusions:1.The intense expression of TNF-αand IFN-γand the positively correlative expression of TNF-α,IFN-γ,TGF-βand IL-10 may play a crucial role in maintaining protective cellular immunoreaction.The relatively strong produce of TNF-αand IFN-γis associated with the local bony resorption in the group of hyperplastic type.2.The severe pathologic injure associated with delayed type hypersensitivity showed in the local tuberculous focus of caseous necrotic type. The strong expression of TGF-βand IL-10 and the maladjusted produce of TNF-α, IFN-γ,TGF-βand IL-10 may be the reason for the aggravation of pathologic injure.The higher expression of TGF-βassociated with lower expression of TNF-αmay contribute to the formation and liquefaction of caseous necrosis in the group of caseous necrotic type.TGF-βand IL-10 also facilitated the medullary fibrosis and bony forming,the medullary fibrosis and bony forming may be helpful to restrict the expansion of tuberculous focus,whereas it may also cause the prolonged bony remodeling in the future.