Ex Vivo Cytokine Release and Pattern Recognition Receptor Expression of Subjects Exposed to Dampness: Pilot Study to Assess the Outcome of Mould Exposure to the Innate Immune System

Abstract

In rooms with moisture damage, the indoor air can be enriched with microorganisms causing a variety of symptoms. Due to the highly diverse composition of bioaerosols and the multiple effects on humans, an assessment of the health risk is not sufficiently possible. The aim of this study was to characterize the features of innate immunity using blood from subjects exposed to moisture damage compared to control subjects living in houses without visible moisture damage. We investigated the expression of TLR-2, TLR-4 and dectin-1 on the surface of monocytes from both fresh blood and after in vitro stimulation with the model substances E. coli endotoxin, zymosan A, Pam3Cys and Aspergillus versicolor in 25 exposed subjects and 25 control subjects. In vitro stimulation of whole blood with the same components was performed for 20 h and the release of inflammatory mediators IL-8 and IL-1β were quantified. In addition to an enhanced number of blood leucocytes, the expression of the receptors TLR-2, TLR-4 and dectin-1 on blood monocytes was significantly enhanced in exposed subjects. In contrast, no different alteration in expression was detected between exposed and control group after in vitro stimulation with the model substances. The release of IL-8 and IL-1β after stimulation of whole blood with A. versicolor was increased in subjects exposed to moisture damage. Furthermore, in the exposed subjects the IL-1β release was significantly enhanced after in vitro stimulation with E. coli endotoxin (1000 pg/mL). In conclusion, features of the innate immune system (receptor expression and mediator release of monocytes) are altered in subjects exposed to moisture damage which may be a potential explanation for the increased incidence of respiratory health diseases observed in these populations.

Moisture damage in home associates with systemic inflammation in children

“…In another study with a longitudinal design, CRP values at the 10‐year follow‐up were not significantly associated with moisture damage or mold at workplace at baseline (Zhang et al., ), but were associated with dampness at home at baseline (Sahlberg et al., ). One recent pilot study found that subjects who were exposed to moisture damage in home had increased expression of TLR‐4, TLR‐2, and dectin‐1 on the cell surface of monocytes in fresh blood and increased stimulated production of inflammatory mediators IL‐1 β and IL‐8, as compared to control subjects, which is well in line with our findings (Punsmann et al., ).…”

“…It has been shown that the indoor moisture damage or microbes originating from moisture damaged building is associated with local airway inflammatory response (Hirvonen et al., ; Huttunen et al., ; Jussila et al., ; Purokivi et al., ; Roponen et al., ). Few studies have also suggested an association between moisture damage and mold and systemic inflammation in humans but they have been very small in sample size (Beijer et al., ; Punsmann et al., ) or used a very limited set of inflammatory markers (Sahlberg et al., ; Zhang et al., ). There are no previous studies on the effect of moisture damage in home on systemic inflammation markers in children.…”

Early age exposure to moisture damage and systemic inflammation at the age of 6 years

“…22 One Finnish study found that working in TA B L E 5 Adjusted associations between early age exposure to moisture damage with or without mold in the child's main living areas and combined levels of unstimulated and stimulated cytokines at the age of 6 years N, number of observations; CRP, C-reactive protein; aOR, adjusted odds ratio; 95%CI, 95% confidence interval; TNF-α, tumor necrosis factor alpha; IL-1b, Interleukin 1-beta; IL-6, Interleukin 6; PI, phorbol 12-myristate 13-acetate and ionomycin stimulated; LPS, lipopolysaccharide stimulated; PPG peptidoglycan stimulated. a Combination variables for IL-1β, IL-6, and TNF-a were created by taking the ranks of the three cytokines without stimulant (unstimulated) and within each stimulates (PI, LPS, and PPG).…”

Determination of ATP-activity as a useful tool for monitoring microbial load in aqueous humidifier samples

“…Methods without culturing are for example DNA sequencing (Nonnenmann et al, 2010), fluorescence analysis using DAPI staining (Klug and Jäckel, 2012), measurement of endotoxin activity with the LAL test (Gee et al, 2008;Liebers et al, 2009), detection of pyrogenic activity with whole blood assay (Liebers et al, 2010;Punsmann et al, 2013), determination of fungi antigen or ␤-glucan by the ELISA technique (Sander et al, 2008(Sander et al, , 2012Zahradnik et al, 2013), and ATP content via bioluminescence (Hammes et al, 2010;Mueller et al, 2009;Liebers et al, 2012).…”

“…Allergic reactions have also been reported Sander et al, 2012). Finally, a recent study suggested that the innate immune system may be affected by exposure to bioaerosols containing molds or other microorganisms (Punsmann et al, 2013). Therefore, it is critical that preventative measures are taken to ensure that the water in the humidifier is routinely cleaned and monitored.…”