Evaluation of chemokines CXCL8 and CCL2, serotonin, and vascular endothelial growth factor serum concentrations in healthy dogs from seven breeds with variable predisposition for canine idiopathic pulmonary fibrosis

Abstract

The West Highland white terrier (WHWT) is particularly prone to canine idiopathic pulmonary fibrosis (CIPF). We hypothesized that higher circulating concentrations of chemokines CXCL8, CCL2, serotonin (5-HT), or vascular endothelial growth factor (VEGF) could serve as predisposing factors for CIPF development in the WHWT breed. Serum samples from 103 healthy dogs of seven different breeds variably predisposed to CIPF were collected. Serum CXCL8 concentrations were higher in healthy WHWT compared with each of the other groups of healthy dogs. Serum CCL2 concentrations were higher in healthy WHWT and Maltese compared with King Charles spaniels and Malinois Belgian shepherds. No relevant inter-breed differences were observed for serum 5-HT concentrations regarding CIPF predisposition. VEGF values from 89.3% of samples tested were below the kit detection limit. In conclusion, high CXCL8 blood concentrations and possibly CCL2 concentrations might be related to the breed predisposition of the WHWT for CIPF and warrants further investigations.

Interbreed variation in serum serotonin (5-hydroxytryptamine) concentration in healthy dogs

“…Pairwise comparisons showed significant differences in 42% of breed comparisons, with Newfoundlands, Belgian Shepherds and CKCSs having the highest serum 5-HT concentrations. Higher serum and platelet-rich plasma 5-HT concentrations have previously been shown in healthy CKCSs compared with other breeds combined [12,13], and interestingly, in a recent study including approximately 100 healthy dogs, CKCSs along with Belgian Shepherds were also among the breeds with the highest serum 5-HT concentrations [24]. However, the Dachshund, which like the CKCS is a breed at risk of developing MMVD [32], was among the breeds with lowest serum 5-HT concentrations in the present study; whereas, the two other breeds with higher 5-HT, Newfoundlands and Belgian Shepherds, are not high-risk breeds for MMVD.…”

“…Canine reference values are lacking, but higher serum and platelet-rich plasma 5-HT concentrations have been found in healthy CKCS dogs compared with healthy dogs of other breeds [12,13]. In another study of healthy dogs, CKCS along with Scottish Terriers, Maltese, and Belgian Shepherds had higher serum 5-HT concentrations than two other terrier breeds and Labrador Retrievers [24].…”

MnTBAP Inhibits Bleomycin-Induced Pulmonary Fibrosis by Regulating VEGF and Wnt Signaling

“…Recent reports indicate that VEGF, a central regulator of angiogenesis, is dysregulated in patients with fibrotic diseases (Smadja et al, ; Bien et al, ; Roels et al, ). Furthermore, VEGF inhibitors have been shown to attenuate bleomycin‐induced pulmonary fibrosis in mice (Ou et al, ; Iyer et al, ).…”

Idiopathic pulmonary fibrosis in West Highland white terriers: An update

“…A targeted approach was used to select other biomarkers, based on their previously demonstrated direct or indirect pro-fibrotic effects, or based on their proven relevance as diagnostic and/or prognostic biomarkers in human IPF. Those biomarkers included procollagen type III amino terminal pro-peptide (PIIINP) (Heikkilä et al, 2013), endothelin-1 (ET-1) (Krafft et al, 2011), transforming growth factor beta-1 (TGF-β1) (Krafft et al, 2014), CCL2 (Roels et al, 2015a,b), IL-8 (Roels et al, 2015a,b), 5-hydroxytryptamine-serotonin (5-HT) (Roels et al, 2015a), vascular endothelial growth factor (VEGF) (Roels et al, 2015a), Krebs Von den Lungen-6 (KL6) (Fastrès et al, 2018) and C-reactive-protein (CRP) (Viitanen et al, 2014). Among those biomarkers, CCL2, IL-8, ET-1 and PIIINP were elevated in the BALF of WHWTs with CIPF compared with healthy WHWTs, while only CCL2 and ET-1 were elevated in the serum of affected WHWTs compared with healthy WHWTs (Krafft et al, 2011;Heikkilä et al, 2013;Roels et al, 2015a,b).…”

“…Among those biomarkers, CCL2, IL-8, ET-1 and PIIINP were elevated in the BALF of WHWTs with CIPF compared with healthy WHWTs, while only CCL2 and ET-1 were elevated in the serum of affected WHWTs compared with healthy WHWTs (Krafft et al, 2011;Heikkilä et al, 2013;Roels et al, 2015a,b). Furthermore, the blood concentrations of IL-8 (Roels et al, 2015a), TGF-β1 (Krafft et al, 2014) and KL6 (Fastrès et al, 2018) were significantly higher in the serum of healthy WHWTs in comparison with healthy agematched dogs from breeds non-predisposed to CIPF. The presence of such high circulating concentrations of these mediators in the predisposed breed is possibly related to, or indicative of the predisposition of the WHWT breed to CIPF.…”