GM‐CSF, IL‐5 and RANTES immunoreactivity and mRNA expression in chronic hyperplastic sinusitis with nasal polyposis (NP)

Abstract

Eosinophils are a prominent feature of chronic hyperplastic sinusitis with nasal polyposis (CHS/NP). Our previous studies showed that their presence was associated with the expression of GM-CSF and RANTES mRNA. In allergic NP, increased expression of IL-5 was also found. We wished to examine cytokine immunoreactivity for IL-5, GM-CSF and RANTES mRNA in allergic and non-allergic NP and compare immunoreactivity with expression of cytokine mRNA by in situ hybridization. NP were obtained from five allergic and eight non-allergic subjects with CHS/NP. Middle turbinate tissue from eight normal subjects were used as controls. Cell-associated cytokine mRNA was detected by in situ hybridization (ISH). Cytokine immunoreactive cells were enumerated by immunostaining. Colocalization immunostaining was also performed to identify specific cell types producing IL-5. Immunostaining for GM-CSF, IL-5 and RANTES protein was increased in both allergic and non-allergic NP compared with control middle turbinates. Allergic polyps contained greater numbers of IL-5 immunoreactive cells (P = 0.01), whereas non-allergic polyps contained greater numbers of GM-CSF immunoreactive cells (P = 0.04). Immunostaining was primarily associated with inflammatory cells, but immunostaining for RANTES and, to a lesser extent GM-CSF, was also seen in the epithelium. The density of immunoreactive cells was variably correlated with cytokine mRNA⁺ cells (GM-CSF: R = 0.56, P = 0.05; IL-5: R = 0.76, P = 0.003; and RANTES: R = 0.89, P = 0.0005). Colocalization immunostaining revealed that the majority of IL-5 immunoreactive cells in both allergic and non-allergic NP were T lymphocytes. However, allergic NP contained greater numbers of IL-5⁺/CD3⁺ T lymphocytes and IL-5⁺ mast cells, whereas non-allergic NP contained greater numbers of IL-5⁺ eosinophils. We conclude that GM-CSF, IL-5 and RANTES are produced in increased amounts in both allergic and non-allergic NP. Distinguishing features of non-allergic NP include fewer numbers of CD3 T lymphocytes, fewer IL-5⁺/CD3⁺ T lymphocytes and greater numbers of IL-5⁺ eosinophils. These differences may suggest different mechanisms of eosinophil accumulation and activation in allergic vs non-allergic NP.