Gokul Raj Kathamuthu1, Nathella Pavan Kumar2, Kadar Moideen3, Dhanaraj Baskaran4, Syed Hissar4, Basavegowdanadoddi M Shrinivasa4, Rathinam Sridhar5, Subash Babu6. 1. National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India. Electronic address: gokul.r@nirt.res.in. 2. National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India. 3. National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India. 4. National Institute for Research in Tuberculosis, Chennai, India. 5. Government Stanley Medical Hospital, Chennai, India. 6. National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Abstract
BACKGROUND: IL-10 family cytokines are associated with the host immune response to pulmonary tuberculosis (PTB), but their association with host response in tuberculous lymphadenitis (TBL) is not known. METHODS: Hence, we examined the circulating levels of the whole panel of IL-10 family cytokines in TBL (n = 44) and compared them to the levels in PTB (n = 44) and healthy control (HC, n = 44) individuals. We also assessed the pre and post-treatment cytokine levels in TBL individuals following the completion of anti-tuberculosis treatment (ATT). Next, we also compared the levels of IL-10 family cytokine in circulation versus lymph node (LN) culture supernatants in a subset of TBL individuals (n = 22). Finally, we also measured the levels of IL-10 family cytokines in tuberculosis antigen (purified protein derivative, PPD) stimulated and unstimulated LN culture supernatants. RESULTS: TBL individuals exhibit significantly decreased levels of IL-10, IL-19, IL-20, IL-24, IL-28B and IL-29 in the circulation when compared to PTB (except IL-10) and HC (except IL-20 and IL-28B) and significantly increased levels of IL-22 when compared to PTB individuals. Following ATT, TBL individuals exhibit significantly elevated levels of IL-10, IL-19, IL-20, IL-24, IL-28B and IL-29 and significantly diminished levels of IL-26. Similarly, TBL individuals also exhibited significantly increased levels of IL-10, IL-19, IL-20, IL-24, IL-28A and IL-29 in LN culture supernatants compared to plasma and significantly decreased levels of IL-22. This was associated with enhanced levels of IL-19, IL-20, IL-24, IL-28B and IL-29 upon PPD stimulation of LN cultures. CONCLUSIONS: Therefore, we demonstrate that TBL is associated with significantly diminished plasma and elevated LN culture supernatant levels of most of the IL-10 family cytokines. This to our knowledge is the first comprehensive examination of IL-10 family cytokines in TBL.
BACKGROUND:IL-10 family cytokines are associated with the host immune response to pulmonary tuberculosis (PTB), but their association with host response in tuberculous lymphadenitis (TBL) is not known. METHODS: Hence, we examined the circulating levels of the whole panel of IL-10 family cytokines in TBL (n = 44) and compared them to the levels in PTB (n = 44) and healthy control (HC, n = 44) individuals. We also assessed the pre and post-treatment cytokine levels in TBL individuals following the completion of anti-tuberculosis treatment (ATT). Next, we also compared the levels of IL-10 family cytokine in circulation versus lymph node (LN) culture supernatants in a subset of TBL individuals (n = 22). Finally, we also measured the levels of IL-10 family cytokines in tuberculosis antigen (purified protein derivative, PPD) stimulated and unstimulated LN culture supernatants. RESULTS:TBL individuals exhibit significantly decreased levels of IL-10, IL-19, IL-20, IL-24, IL-28B and IL-29 in the circulation when compared to PTB (except IL-10) and HC (except IL-20 and IL-28B) and significantly increased levels of IL-22 when compared to PTB individuals. Following ATT, TBL individuals exhibit significantly elevated levels of IL-10, IL-19, IL-20, IL-24, IL-28B and IL-29 and significantly diminished levels of IL-26. Similarly, TBL individuals also exhibited significantly increased levels of IL-10, IL-19, IL-20, IL-24, IL-28A and IL-29 in LN culture supernatants compared to plasma and significantly decreased levels of IL-22. This was associated with enhanced levels of IL-19, IL-20, IL-24, IL-28B and IL-29 upon PPD stimulation of LN cultures. CONCLUSIONS: Therefore, we demonstrate that TBL is associated with significantly diminished plasma and elevated LN culture supernatant levels of most of the IL-10 family cytokines. This to our knowledge is the first comprehensive examination of IL-10 family cytokines in TBL.
Authors: G Gallagher; H Dickensheets; J Eskdale; L S Izotova; O V Mirochnitchenko; J D Peat; N Vazquez; S Pestka; R P Donnelly; S V Kotenko Journal: Genes Immun Date: 2000-10 Impact factor: 2.676
Authors: Ian A Myles; Natalia M Fontecilla; Patricia A Valdez; Paul J Vithayathil; Shruti Naik; Yasmine Belkaid; Wenjun Ouyang; Sandip K Datta Journal: Nat Immunol Date: 2013-06-23 Impact factor: 25.606
Authors: Heike C Hawerkamp; Lasse van Geelen; Jan Korte; Jeremy Di Domizio; Marc Swidergall; Afaque A Momin; Francisco J Guzmán-Vega; Stefan T Arold; Joachim Ernst; Michel Gilliet; Rainer Kalscheuer; Bernhard Homey; Stephan Meller Journal: Sci Rep Date: 2020-10-14 Impact factor: 4.379