title: Clinical significance of serum Th1-, Th2- and regulatory T cells-associated cytokines in adult T-cell leukemia/lymphoma: high interleukin-5 and -10 levels are significant unfavorable prognostic factors.
abstract: Patients with adult T-cell leukemia/lymphoma (ATLL) are in a severely immunocompromised state. Therefore, it is assumed that ATLL cells either express particular cytokines or induce their expression in host immune cells, disrupting the balanced production of cytokines and causing the host's immune system to break down. We examined the levels of serum cytokines including T helper type 1- (Th1-) associated cytokines [IFN-gamma, TNF-alpha, and interleukin (IL)-2], Th2-associated cytokines (IL-4, -5 and -6) and regulatory T cell-associated cytokines (IL-10 and TGF-beta1) in 94 ATLL patients, 39 asymptomatic human T-cell lymphotropic virus type-1 (HTLV-1) carriers and 50 healthy adult volunteers, to clarify whether elevated levels of particular cytokines are associated with the prognosis of ATLL patients. On multivariate analysis, high IL-5 and IL-10 levels were independent and significant unfavorable prognostic factors among the ATLL patients. The IL-10 level significantly increased with disease progression at each step from asymptomatic HTLV-1 carrier to ATLL of the indolent variant (chronic and smoldering subtypes) to ATLL of the aggressive variant (acute and lymphoma subtypes). Furthermore, high IL-10 was significantly associated with high lactate dehydrogenase (LDH), indicating that the IL-10 level reflects the tumor burden. The IL-5 level was not associated with disease progression nor LDH. Among ATLL patients with the aggressive variant, high IL-5, but not high IL-10, was an independent and significant unfavorable prognostic factor on multivariate analysis. Measurement of serum IL-5 and IL-10 levels is useful for predicting the prognosis and for determining a suitable treatment strategy for ATLL patients.
authors.affiliation: Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya-shi, Aichi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inagaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ishii
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.forename: Jianmin
authors.initials: J
authors.lastname: Ding
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yonekura
authors.forename: Shogo
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Takatsuka
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood*; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015458:Leukemia, T-Cell / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase