Dual Role of Interleukin-10 in Murine Lyme Disease: Regulation of Arthritis Severity and Host Defense

Abstract

In the murine model of Lyme disease, C3H/He mice exhibit severe arthritis while C57BL/6N mice exhibit mild lesions when infected withBorrelia burgdorferi. Joint tissues from these two strains of mice harbor similar concentrations of B. burgdorferi, suggesting that the difference in disease severity reflects differences in the magnitude of the inflammatory response to B. burgdorferi lipoproteins. Stimulation of bone marrow macrophages from C3H/HeN mice with the B. burgdorferi lipoprotein OspA resulted in higher-level production of the inflammatory mediators tumor necrosis factor alpha, nitric oxide, and interleukin-6 (IL-6) than that of macrophages from C57BL/6N mice. In contrast, macrophages from C57BL/6N mice consistently produced larger amounts of the anti-inflammatory cytokine IL-10 than did C3H/HeN macrophages. Addition of recombinant IL-10 suppressed the production of inflammatory mediators by macrophages from both strains. IL-10 was found to modulateB. burgdorferi-induced inflammation in vivo, since C57BL/6J mice deficient in IL-10 (IL-10−/−) developed more severe arthritis than wild-type C57BL/6J mice. The increase in arthritis severity was associated with a 10-fold decrease in the number ofB. burgdorferi organisms present in ankle tissues from IL-10−/− mice. These findings suggest that in C57BL/6 mice, IL-10-dependent regulation of arthritis severity occurs at the expense of effective control of bacterial numbers.

Cytokines in Lyme borreliosis: lack of early tumour necrosis factor‐α and transforming growth factor‐β1 responses are associated with chronic neuroborreliosis

“…20 Several studies have shown an association of TNF-a responses with severe symptoms in experimental Borrelia infections, whereas mild disease correlates with lower levels or even lack of TNF-a. [21][22][23] On the other hand, TNF-a secretion, although potentially harmful, may be necessary for eliminating B. burgdorferi, since inability to produce TNF-a was demonstrated in susceptible mice. 24 Previous studies of serum TNF-a in human Lyme borreliosis have shown divergent results, ranging from high 25 to undetectable levels of TNF-a.…”

Secretion of growth factors from macrophages when cultured with microparticles

“…Macrophages were isolated using the methods published previously. 30 Briefly, bone marrow from the femur of C57 BL/6 mice was flushed with 10 mL RPMI media containing 10% FBS and 30% L929-conditioned medium (macrophage expansion medium; see below) using a 27 G needle and 5 mL syringe. The cell pellets were dispersed by gently pipetting the suspension using the syringe.…”

“…Primary murine macrophages from bone marrow are expanded in vitro either by using L929 supernatants or recombinant macrophages-colony stimulating factor (rM-CSF) or by thioglycolate elicitation from the peritoneum. 30 This study utilized expansion of macrophages from murine bone marrow using L929 supernatants, as this method has been shown to consistently produce high yields of pure macrophage cultures with properties that are similar to those produced using rM-CSF, which is more expensive. 31,32 L929 supernatants were obtained using previously established ORIGINAL ARTICLE JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | NOV 2013 VOL 101A, ISSUE 11 protocols.…”

“…31,32 L929 supernatants were obtained using previously established ORIGINAL ARTICLE JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | NOV 2013 VOL 101A, ISSUE 11 protocols. 30 Briefly, L929 cells were cultured in 5 mL RPMI supplemented with 10% FBS, using a T-25 flask. When the cells reached 75% confluence the cells were trypsinized and replated in a T-75 flask.…”

“…The phenotype is consistent with primary murine macrophages and is similar to the phenotypes obtained by murine macrophages expanded using MCSF or by thioglycolate elicitation from the peritoneum. 30…”