Is in vitro cytokine release a suitable marker to improve the diagnosis of suspected mold-related respiratory symptoms? A proof-of-concept study

Indoor mold infestation can lead to a variety of adverse health effects, including allergic and non-allergic respiratory complaints. Especially if no evidence of an allergic reaction can be found for the complaints, diagnostic tools that might explain mold-associated health problems are missing. As a proof-of-concept, in the present study whole blood assay (WBA) was used to determine cellular response by measuring cytokine release (IL-1β and IL-8) after in vitro stimulation. Blood was available from a total of 48 subjects. By questionnaire, complaints and possible mold exposure were documented. Specific in vitro blood stimulation was tested with endotoxin and extracts of different molds ( , , , and ). To characterize the relevance of WBA in describing the mold-induced immune response, we compared the following groups: asthmatics vs. non-asthmatics, mx1-sensitized vs. non-mx1-sensitized, mold-exposed vs. non-mold-exposed. In response to endotoxin stimulation, a significantly higher IL-1β release was found in mx1-sensitized than in non-mx1-sensitized subjects. Furthermore, the blood of asthmatics showed significantly higher IL-8 and IL-1β release after stimulation with and endotoxin, respectively, compared to non-asthmatics. However, no significant difference in the level of cytokine release was observed between the mold-exposed and non-exposed group, neither after endotoxin nor mold stimulation. In conclusion, the WBA used in this study is not a suitable tool for clinical routine diagnostic workup. Our data suggests that WBA reflects cellular differences that are disease-related but not directly attributable to mold exposure. However, in combination with further data, WBA will be a helpful und interesting tool in research, e.g., in description of the complex immune response to molds.