Propranolol as a modulator of M2b monocytes in severely burned patients

Abstract

A role of immunosuppressive M2 monocytes (IL-12(-)IL-10(+)) on the increased susceptibility of severely burned patients to various opportunistic pathogens has been described. Among M2 monocyte subpopulations, M2b monocytes (IL-17(-)CCL1(+)CXCL13(-)) are predominantly present in the peripheral blood of severely burned patients. In the present study, the rise and fall of M2b monocytes were examined in severely burned patients treated with propranolol. Catecholamine is known as an inducer of M2 monocytes, and propranolol is a competitive blocker of catecholamine binding to β-adrenergic receptors. Twenty-two children with 30% or more TBSA burn were enrolled in the study. Propranolol at a dose of 4 mg/kg/day was administered to these patients by feeding-tube or mouth. Burn patient monocytes exhibited weak bactericidal activity. IL-12 was produced by propranolol-treated patient monocytes after stimulation with Staphylococcus aureus antigen, and the production of IL-10, CCL1, CCL17, or CXCL13 by these monocytes was not demonstrated. These results indicate that a predominance of M2b monocytes in severely burned patients is intervened by the propranolol treatment. The increased susceptibility, to be associated with the appearance of M2b monocytes, of severely burned patients to opportunistic pathogens might be controlled by propranolol.

Palmitate differentially regulates the polarization of differentiating and differentiated macrophages

“…Catecholamines are believed to play a significant role in M2 polarization in burn patients. 9 Other factors like IL-10, glucocorticoid, hormones, apoptotic cells, immune complexes, all of which are increased in critical illness, can also polarize macrophages to an M2-like phenotype. 26 Our results demonstrate that in addition to the factors mentioned above, hyperglycaemia and hyperlipidaemia can also modify the phenotype of macrophages.…”

“…[1][2][3] Critically ill patients present with various lipid disorders: high levels of triglycerides and free fatty acids (FFA); low levels of low-density lipoproteins; and low levels of high-density lipoproteins. 4 Increased lipolysis after burn injuries causes increased circulating triglycerides and FFA levels, These M2 macrophages inhibit conversion from resident macrophage to M1; 9,10 however, the mechanisms underlying M2 dominance in these tissues in critical illness are not fully understood.…”

Nerve Driven Immunity: Noradrenaline and Adrenaline

“…On the other side, reversal of the inhibitory effects of noradrenaline and adrenaline on human monocytes may result in immunostimulation. In agreement with this hypothesis, recently the b 2 -AR antagonist propranolol has been shown to reduce circulating immunosuppressive M2b monocytes in severely burned children, suggesting that the increased susceptibility of severely burned patients to opportunistic pathogens might be controlled by propranolol (Kobayashi et al 2011).…”

“…The therapeutic effects of a 2 -AR antagonism or pharmacological inhibition of catecholamine synthesis in rodent models of acute lung injury has been discussed previously (Flierl et al 2007(Flierl et al , 2009. Recently, it has been shown that the b-AR antagonist propranolol may control the susceptibility of severely burned patients to opportunistic pathogens by reducing the occurrence of immunosuppressive M2 monocytes (Kobayashi et al 2011).…”

Monitoring Neutrophil-Expressed Cell Surface Esophageal Cancer Related Gene-4 after Severe Burn Injury

“…The kinetics of cytokine and cell surface marker expression post-injury have been studied widely in human leukocytes after injury [15][16][17][18]. Yet the predictive power of global genetic changes has been disappointing [4,5].…”