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Lipopolysaccharide suppresses cytokine release from coxsackie virus-infected human monocytes
A Henke1, H P Spengler, A Stelzner
1Institute of Immunology, Philipps University, Marburg, Germany.
Insights
Coxsackie virus B3 (CVB3) activates human monocytes, leading to cytokine release and reduced reactivity to other stimuli. This immune cell response may contribute to chronic myocarditis development.
Area of Science:
- Immunology
- Virology
- Cardiology
Background:
- Coxsackie virus B3 (CVB3) infections are linked to increased mononuclear leukocyte infiltration in tissues.
- Monocytes/macrophages play a key role in CVB3-induced myocarditis by sustaining chronic inflammation.
Purpose of the Study:
- To investigate the susceptibility and reactivity of human monocytes to CVB3 infection.
- To understand how CVB3 affects monocyte activation and response to lipopolysaccharide (LPS).
Main Methods:
- Freshly isolated human monocytes were exposed to varying doses of CVB3 (0.1-10 MOI).
- Monocytes were treated with CVB3 alone or in combination with macrophage-activating lipopolysaccharide (LPS).
- Monocyte adherence, cytokine release (TNF-α, IL-1β, IL-6), and prostaglandin E2 (PGE2) secretion were measured.
Main Results:
- CVB3 infection alone activated monocytes, increasing adherence and releasing cytokines and PGE2.
- Simultaneous LPS addition suppressed TNF-α and PGE2 production in CVB3-infected monocytes.
- LPS partially inhibited IL-1β release but did not affect IL-6 synthesis.
Conclusions:
- CVB3 activates monocytes to produce cytokines but impairs their responsiveness to further stimuli.
- Persistent CVB3-induced cytokine release and monocyte unresponsiveness may contribute to chronic myocarditis.
Abstract:
Infections by coxsackie virus B3 (CVB3) have been reported to be associated with an enhanced influx of mononuclear leukocytes into afflicted tissue. Current evidence indicates that monocytes/macrophages are specifically involved in CVB3-induced myocarditis by maintaining a chronic inflammatory response. To examine susceptibility and reactivity to CVB3, freshly isolated human monocytes were exposed to various virus doses (0.1-10 MOI) in the presence or absence of macrophage-activating lipopolysaccharide (LPS). CVB3 infection alone induced an activation of monocytes as evidenced by enhanced adherence, release of cytokines and secretion of prostaglandin E2 (PGE2). Simultaneous addition of LPS almost entirely suppressed LPS-specific production of tumour necrosis factor alpha (TNF alpha) and PGE2, partially inhibited release of interleukin 1 beta (IL 1 beta) and did not affect interleukin 6 (IL6) synthesis of CVB3-infected monocytes. These data show that CVB3 activates monocytes to cytokine production but renders them unreactive to further activating stimuli. Further studies should determine the extent to which continuous cytokine release from persistently CVB3-infected monocytes, and their apparent unresponsiveness to other stimuli, contribute to chronic myocarditis.