Phagocyte dysfunction in polymyalgia rheumatica and other age-related, chronic, inflammatory conditions

Abstract

This study was conducted to evaluate phagocyte function in patients with age-related chronic inflammatory conditions. It included 95 patients with PMR, 17 with GCA, 40 with EORA, and 25 age-matched HCs. Serum IL-8 was determined with a bead array. The chemotactic capacity, phagocytic ability, and oxidative burst activity of circulating leukocytes were determined with flow cytometry kits. Patients with active chronic inflammatory diseases showed a significant increase in circulating levels of IL-8 that remained elevated in patients with PMR or EORA, despite treatment. No correlation was found between circulating IL-8 and the migratory capacity of neutrophils. Neutrophils from patients with active EORA without stimulus and after fMLP stimuli showed a higher capacity to migrate than those of the HCs (P=0.033). The phagocytic activity of granulocytes in the patients with GCA was significantly higher than in the HCs and the patients with PMR or EORA (P<0.05). The percentage and MFI of phagocytes that produce ROIs when stimulated with Escherichia coli was significantly reduced in neutrophils and monocytes from the patients with age-restricted inflammatory conditions. We concluded that the effector functions of phagocytes, determined to be chemotaxis, phagocytosis, and oxidative burst, are deregulated in age-restricted inflammatory disorders and may have a pathogenic role.

Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury

“…In age-related chronic inflammatory conditions, several functions of mononuclear phagocytes, including immune defense, inflammation, and phagocytosis, are deregulated [40]. In the current study, the reduced LPS-stimulated MCP-1 and IL-6 expression in the diabetic macrophages (Figure 4) provided a mechanistic link between impaired mononuclear phagocyte function and diabetes-induced exacerbation of ischemic injury.…”

“…Because the chronic inflammation is associated with compromised antimicrobial defenses, delayed wound healing, and impaired inflammatory responses [2,40], immunological disturbances may be an underlying event for diabetes-induced exacerbation of ischemic brain injury. Diabetic mice ( db/db ) displayed reduced inflammatory cytokine expression and microglial activation and delayed wound healing [41].…”

Involvement of Monocyte Subsets in the Immunopathology of Giant Cell Arteritis

“…This is an unexpected finding as the accumulated glucocorticoid dose is substantially lower in PMR patients. An unexplored possibility is that classical monocytes in PMR are more sensitive to glucocorticoid treatment due to their altered characteristics; a previous study showed an altered functionality of monocytes from PMR patients when compared with monocytes from GCA patients and controls 49 .…”

Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults

“…This includes extended lifespan and increased inflammatory cytokine and chemokine production augmenting the inflammatory milieu ( Raza et al, 2006 , Cross et al, 2004 , Parsonage et al, 2008 ). Migratory activity is also altered in these conditions with cells becoming more adherent ( Álvarez-Rodríguez et al, 2013 , Aglas et al, 1998 , Paino et al, 2011 , Stockley et al, 2013 ). Increased systemic inflammation with age, inflammaging, has been well documented and we observed higher systemic inflammation in the older group as a whole compared to the young.…”