Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-α) receptors in type C chronic liver disease

Abstract

SUMMARYWe previously reported that the number of TNF-a-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-aRI (p55) and -aRII (p75), and IL-10, all of which act as TNF-a buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-aR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-aRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-aRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.

Trans-Presentation of IL-15 Dictates IFN-Producing Killer Dendritic Cells Effector Functions

“…T cell-dependent delayed type hypersensitivity responses are impaired in IL-15 Ϫ/Ϫ mice but restored by injection of IL-15 producing WT DC in vivo (36). Furthermore, IL-15 could mediate deleterious effects and has been involved in the exacerbation of numerous inflammatory processes, such as rheumatoid arthritis (37,38), inflammatory bowel disease (39,44,45), type C chronic hepatitis (40), sarcoidosis (41), multiple sclerosis (42), and celiac disease (43). Elevated IL-15 production and IL-15 producing cells were identified as potential initiators of the inflammation.…”

Natural, Proteolytic Release of a Soluble Form of Human IL-15 Receptor α-Chain That Behaves as a Specific, High Affinity IL-15 Antagonist

“…Inasmuch as IL-15R␣ transcripts are expressed by many cell types and tissues, and as sIL-15R␣ displays high affinity and IL-15 blocking efficiency in vitro, this soluble receptor can be anticipated to exert an important role in physiology and pathology. IL-15 has been detected in the biological fluids of patients with chronic inflammatory diseases such as rheumatoid arthritis (39), inflammatory bowel diseases (40), pulmonary diseases (41), and chronic active hepatitis (42). The availability of specific RIAs able to measure the levels of sIL-15R␣ (this study) and IL-15-sIL-15R␣ complex (E. Mortier, unpublished observations) will enable a better analysis of the regulation of the IL-15 system in such diseases.…”

Autocrine IL-15 Mediates Intestinal Epithelial Cell Death Via the Activation of Neighboring Intraepithelial NK Cells

“…(45), Mycobacterium tuberculosis, Toxoplasma gondii (46), Listeria monocytogenes (47), HIV (48,49), or hepatitis C virus (50). It was reported that after oral infection of rats with L. monocytogenes, the level of IL-15 production by IECs was up-regulated and the numbers of CD3 Ϫ NK ϩ IELs also were increased (47).…”