Follow-up MARCoNS culture status linked to α-MSH levels in chronic inflammatory response syndrome cohort

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Frontiers in Medicine Published April 19, 2026 Medically reviewed May 1, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider that MARCoNS-negative status may be associated with higher α-MSH levels in CIRS, but findings are associative and require prospective validation.

This retrospective observational cohort study included 188 adult patients evaluated within a CIRS-informed clinical framework at a single clinical site. The study examined longitudinal trajectories of α-MSH, matrix metallopeptidase-9 (MMP-9), and vasoactive intestinal polypeptide (VIP) across two timepoints of laboratory data, comparing patients based on follow-up MARCoNS culture status (negative vs positive).

Patients who were MARCoNS-negative at follow-up exhibited higher circulating α-MSH levels compared with those who remained positive. Across the full cohort, α-MSH increased by an estimated 10 pg/mL between baseline and follow-up, with a significant timepoint-by-MARCoNS interaction (p-value not reported). For MMP-9, no corresponding MARCoNS interaction was observed; MMP-9 decreased by 398 ng/mL across the cohort. For VIP, no corresponding MARCoNS interaction was observed; VIP increased by 20 pg/mL across the cohort.

Safety and tolerability data were not reported. Key limitations include the retrospective design, single clinical site, only two timepoints per participant, and no control for confounding variables. The practice relevance is that findings support further prospective investigation into links between persistent bacterial nasal colonization and neuroendocrine-immune biomarkers. Causality is not established; this is an association only, not causation.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

IntroductionNeuroimmune regulatory peptides play central roles in coordinating inflammatory, metabolic, and mucosal immune processes in humans. Among these, α-melanocyte stimulating hormone (α-MSH), a proopiomelanocortin-derived peptide, has been implicated in modulation of cytokine signaling, epithelial barrier function, and pain processing. However, determinants of circulating α-MSH levels in chronic inflammatory states remain incompletely characterized in human clinical populations. Persistent sinonasal colonization with multiple antibiotic-resistant coagulase-negative staphylococci (MARCoNS) has been reported in some cohorts presenting with environmentally associated multisystem illness, described in some clinical settings as Chronic Inflammatory Response Syndrome (CIRS). Yet its relationship to systemic neuroendocrine biomarkers has not been quantitatively examined.MethodsThis retrospective observational cohort study examined whether follow-up MARCoNS culture status was associated with longitudinal trajectories of α-MSH, compared with two additional biomarkers commonly assessed in this population: matrix metallopeptidase-9 (MMP-9) and vasoactive intestinal polypeptide (VIP). A total of 188 adult patients evaluated within a CIRS-informed clinical framework at a single clinical site were included. Each participant contributed two timepoints of laboratory data for α-MSH, MMP-9, and VIP, along with MARCoNS culture results.ResultsAcross the full cohort, α-MSH increased by an estimated 10 pg/mL, MMP-9 decreased by 398 ng/mL, and VIP increased by 20 pg/mL between baseline and follow-up. Mixed-effects modeling revealed a significant timepoint-by-MARCoNS interaction for α-MSH, such that patients who were MARCoNS-negative at follow-up exhibited higher circulating α-MSH levels compared with those who remained positive. In contrast, no corresponding MARCoNS interaction was observed for VIP or MMP-9.DiscussionThese findings provide quantitative evidence that follow-up MARCoNS culture status is selectively associated with α-MSH trajectories in this retrospective cohort, supporting further prospective investigation into potential links between persistent bacterial nasal colonization and neuroendocrine-immune biomarkers in multisystem chronic illness.