Markers of innate immune activity in patients with type 1 and type 2 diabetes mellitus and the effect of the anti-oxidant coenzyme Q10 on inflammatory activity

Abstract

SummaryMajor long-term complications in patients with diabetes are related to oxidative stress, caused by the hyperglycaemia characteristic for diabetes mellitus. The anti-oxidant coenzyme Q10 (CoQ10) has therefore been proposed as a beneficial supplement to diabetes treatment. Apart from its anti-oxidative function, CoQ10 appears to modulate immune functions by largely unknown mechanisms. The aim of this study was therefore to investigate the effect of CoQ10 on antimicrobial peptides and natural killer (NK) cells, both innate immune components implicated in the pathogenesis of diabetes and diabetes-associated long-term complications such as cardiovascular disease. We determined serum levels of antimicrobial peptides and the phenotype of NK cells isolated from peripheral blood of patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) and from healthy controls. In addition, the same parameters were determined in diabetic patients after a 12-week period of CoQ10 supplementation. Two antimicrobial peptides, the human cathelicidin antimicrobial peptide (CAMP) and the human beta defensin 1 (hBD1), were reduced in serum from patients with T1DM. This defect was not reversible by CoQ10 supplementation. In contrast, CoQ10 reduced the levels of circulating hBD2 in these patients and induced changes in subset distribution and activation markers in peripheral NK cells. The results of the present study open up novel approaches in the prevention of long-term complications associated to T1DM, although further investigations are needed.

Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an increased production of interleukin (IL)-1β via the nucleotide-binding domain and leucine-rich repeat containing family pyrin 3(NLRP3)-inflammasome activation: a possible implication for therapeutic decision in these patients

“…In recent years, the involvement of innate immunity has been suggested in the pathogenesis of T2D [23][24][25][26][27][28][29][30], and several studies have described elevated circulating levels of acute-phase proteins, cytokines and chemokines in patients with T2D, and elevated levels of IL-1b, IL-6 and C-reactive protein have been suggested as predictive factors of T2D development [36][37][38][39]. In addition, an immune cell infiltration surrounding the pancreatic islets in human T2D, characterized largely by MO, may be observed [39].…”

“…In addition, an immune cell infiltration surrounding the pancreatic islets in human T2D, characterized largely by MO, may be observed [39]. On this basis, a better knowledge of the metabolically driven inflammation observed in T2D may open future perspectives, identifying new potential biomarkers and/or new therapeutic targets [23][24][25][26][27][28][29][30]. In this regard, several papers have suggested, both in experimental models and in humans, the usefulness of cytokine antagonism therapies Monocytes were incubated with 11 mmol/1 glucose (11G) and 33 mmol/1 glucose (33G) for 24 h. Our data showed that, after 24 h of incubation with 11G, a significant increase of relative IL-1b and TNF mRNA expressions were reported when type 2 diabetes (T2D), rheumatoid arthritis (RA) and T2D/RA patients were compared with healthy controls (HC) (P < 0Á001 for each comparison).…”

“…In recent years, many papers have supported the role of inflammatory mechanisms in the pathogenesis of T2D [23] and recently, as already described for type 1 diabetes mellitus (T1D), the pathogenetic role of insulitis in T2D has been proposed [23][24][25][26]. Although the precise aetiology of the insulitis in both types of diabetes remains to be understood fully, some specific differences have been described.…”

“…Different pathological stimuli are able to modulate the assembly of a cytosolic platform, the inflammasome, composed of at least five different protein components integral to this complex, including nucleotide-binding domain and leucine-rich repeat containing family pyrin 3(NLRP3), caspase recruitment domain containing protein 8 (CARD8), pyrin, apoptosis-associated speck-like protein containing CARD (ASC) and pro-caspase-1, which is involved mainly in host defence against microbes and where the inactive pro-IL-1b is cleaved into a small, mature, active form [29,30]. NLRP3-inflammasome is also activated by host-derived metabolites, such as monosodium urate crystals, cholesterol crystals and free fatty acids, and involved in the development of some inflammatory diseases such as gout, atherosclerosis and T2D [23][24][25][26][27][28][29][30].…”

Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota

“…Indeed, around the age of weaning, neutrophils transiently infiltrate the pancreas and produce cathelicidins activating IFN-a-secreting pDCs. However, the concentration of cathelicidins has been shown to be reduced in the serum of patients with autoimmune type 1 diabetes (T1D) compared with healthy subjects suggesting an additional role of cathelicidins in T1D (Brauner et al, 2014). Regarding the various potential source of cathelicidins in peripheral tissues (non-immune versus immune cells) and the opposing immunomodulatory roles of cathelicidins (pro-versus anti-inflammatory), we addressed the question of whether cathelicidins are produced by non-immune cells in the pancreas and might influence the pancreatic immune environment in the context of autoimmune diabetes in NOD mice.…”