RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal peptide (VIP) shows a shift in metabolic state and innate immune functions that coincide with healing

Abstract

Exposure to the microbial growth in Water Damaged Buildings (WDB) can result in a chronic, multi-symptom, multisystem illness, which can last years, termed Chronic Inflammatory Response Syndrome (CIRS). Symptoms of CIRS include but are not limited to fatigue, respiratory problems, including cough, interstitial lung disease and asthma-like conditions; executive cognitive deficits, neurologic deficits, pain and gastrointestinal distress among others. There are published treatment options for CIRS patients but relatively little is known about the genomic basis of the illness. One of the most striking features of CIRS is the absence of the anti-inflammatory neuropeptides vasoactive intestinal peptide (VIP) and melanocyte stimulating hormone (MSH). Additionally, the master immune regulator, TGFb1 is abnormally high in most patients. This study surveyed 15 patients coming to a specialized clinic for CIRS with refractory symptoms, despite use of a published treatment protocol, who agreed to have their transcriptomes monitored while receiving off label, exogenous VIP nasal spray treatments. Several key immune regulators were found to be differentially expressed over the course of treatment with VIP, such as CD244, CD3D, CD48 and CD52, granzymes, defensins, and the Ikaros family of lymphoid transcription factors. In addition to down regulated innate immune functions, there appears to be an overall metabolic shift, with a down regulation of ribosomal and mitochondrial gene expression, possibly indicating a calming of components of immune responses.  Understanding the need for accurate diagnosis of CIRS in order to effectively treat patients, this transcriptomic study sheds important light on new aspects of pathophysiology.