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Opposing effects of interleukin-10 on mouse macrophage functions
1Centro de Citologia Experimental, University of Porto, Portugal.
Insights
Interleukin-10 (IL-10) has complex effects on macrophage function. This study reveals IL-10 can both inhibit and promote macrophage responses, depending on the timing of cytokine and agonist exposure.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Interleukin-10 (IL-10) is typically viewed as a macrophage deactivating factor, suppressing cell-mediated immunity against intracellular parasites.
- Understanding the precise role of IL-10 in modulating macrophage functions is crucial for developing targeted immunotherapies.
Purpose of the Study:
- To investigate the in vitro effects of IL-10 on key macrophage functions, specifically reactive oxygen species (ROS) release, nitric oxide (NO2-) secretion, and anti-mycobacterial activity.
- To determine how the timing of IL-10 exposure relative to other stimuli influences these macrophage responses.
Main Methods:
- Primary mouse bone marrow-derived macrophages were cultured in vitro.
- Macrophages were treated with IL-10, gamma interferon (IFN-gamma), and specific agonists in varying sequences.
- Macrophage functions assessed included O2- release, NO2- secretion, and bacteriostasis of Mycobacterium avium.
Main Results:
- IL-10 inhibited IFN-gamma-induced priming for enhanced O2- release in macrophages.
- The effect of IL-10 on NO2- secretion was dependent on the sequence of IL-10 and NO2- agonist treatment, showing opposing effects.
- IL-10 induced moderate bacteriostasis of Mycobacterium avium and also inhibited IFN-gamma-mediated bacteriostasis.
Conclusions:
- The functional impact of IL-10 on macrophages is context-dependent, varying with the timing of exposure to other cytokines and agonists.
- IL-10 exhibits multifaceted regulatory roles in macrophage immune responses, challenging its simple classification as solely a deactivating factor.
- These findings highlight the importance of temporal dynamics in cytokine signaling for macrophage effector functions.
Abstract:
Interleukin (IL)-10 generally is considered a macrophage deactivating factor and thus inhibits the cell-mediated responses against intracellular parasites. We evaluated the in vitro effects of IL-10 on three different parameters of macrophage function. We found that IL-10 inhibited gamma interferon (IFN-gamma) priming for enhanced O2- release of mouse bone marrow-derived macrophages but had opposing effects on NO2- secretion according to the sequence of the treatment with IL-10 and the agonists of NO2- secretion. Likewise, IL-10 was able to induce a small but consistent degree of bacteriostasis of Mycobacterium avium and, also, to inhibit the bacteriostasis induced by IFN-gamma. Thus, we show that, according to the timing of exposure of macrophages to stimulating and inhibiting cytokines and agonists of their functions, IL-10 shows different effects on macrophage function.
