Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings

Ritchie C Shoemaker,Dennis House,James C Ryan

doi:10.4236/health.2013.53053

Abstract

Exposure in water-damaged buildings (WDB) to airborne bioaerosols including metabolic products of toxigenic fungi, bacteria and actinomycetes; and inflammagens, can lead to a persistent innate immune inflammatory illness. This illness, termed a chronic inflammatory response syndrome (CIRS-WDB), is systemic with symptoms acquired from multiple organ systems. Treatment of CIRS-WDB has progressed rapidly as a better understanding of the inflammatory pathophysiology has led to targeted, sequential therapies. The fundamental basis of uncontrolled innate immune responses, the humoral deficiency of regulatory neuropeptides melanocyte stimulating hormone (MSH) or vasoactive intestinal polypeptide (VIP), seen in over 98% of pa tients, has not consistently responded to any treatment modality. Use of replacement VIP has been attempted anecdotally; VIP replacement therapies show promise in short term studies but longer therapies have not been attempted. Here we report an open label trial of 20 patients with refractory CIRS-WDB illness who took replacement VIP in a nasal spray for at least 18 months with confirmation of durable efficacy and absence of significant side effects. These 20 patients were similar in symptoms and lab find- ings to three previously published cohorts in- volving 1829 patients and 169 controls. Dosage of VIP was titrated downwards from four to zero doses a day to determine minimum effective dose, and retitrated upwards for maximum improvement over time. The trial showed that VIP therapy safely 1) reduced refractory symptoms to equal controls; 2) corrected inflammatory parameters C4a, TGF beta-1, VEGF, MMP9; 3) corrected estradiol, testosterone and 25-OH Vitamin D; 4) returned pulmonary artery systolic pressure (PASP) during exercise to normal; and 5) enhanced quality of life in 100% of trial patients. Subsequent identification of correction of T-regulatory cell levels supports the potential role of VIP in both innate and adaptive immune function.

Highlights

Treatment of the multisystem, multisymptom illness acquired following exposure to the interior environment of buildings with a history of water intrusion and subsequent microbial growth (i.e. WDB) remained problematic until recent years because 1) no consistent pathophysiological mechanisms had been demonstrated; and 2)no biomarkers were consistently identified thereby preventing confirmatory laboratory diagnosis
Cases were similar at baseline to known cases of Chronic Inflammatory Response Syndrome (CIRS)-WDB in large cohorts previously published [5,6] with excessive numbers of symptoms in cases compared to controls (Table 1) and multiple laboratory abnormalities (Table 1) in cases compared to controls
This cohort is clearly affected by an innate immune inflammatory process with nearly 23 health symptoms at baseline; marked reduction in Vasoactive Intestinal Polypeptide (VIP) and MSH; significant elevation of C4a, MMP9 and TGF beta-1; evidence of increased activity of aromatase with reduction of testosterone and elevated estradiol in males but not females; and reduced Vitamin D3 levels

Summary

Introduction

Multisymptom illness acquired following exposure to the interior environment of buildings with a history of water intrusion and subsequent microbial growth (i.e. WDB) remained problematic until recent years because 1) no consistent pathophysiological mechanisms had been demonstrated; and 2)no biomarkers were consistently identified thereby preventing confirmatory laboratory diagnosis. Multisymptom illness acquired following exposure to the interior environment of buildings with a history of water intrusion and subsequent microbial growth (i.e. WDB) remained problematic until recent years because 1) no consistent pathophysiological mechanisms had been demonstrated; and 2). Following publication of reports from the US GAO in 2008 [1], WHO in 2009 [2] and the Consensus Statement of Treating Physicians in 2010 [3], the role of chronic inflammation as a response to exposure has been recognized, providing for effective therapies to control most illness parameters. These therapies did not provide protection from relapse upon reexposure to WDB; some patients remained severely affected. This illness has been called a chronic systemic inflammatory illness (CIRS-WDB, [3]), paralleling a similar OPEN ACCESS. Shoemaker et al / Health 5 (2013) 396-401 description of ciguatera, a biotoxin-associated illness [4]

Results

Discussion

Conclusion