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


OBJECTIVE
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. Methods 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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
D L
DL
Hamilos
D Y
DY
Leung
D P
DP
Huston
A
A
Kamil
R
R
Wood
Q
Q
Hamid
D001249:Asthma / Q000378:metabolism / Q000473:pathology; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D004804:Eosinophils / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D010256:Paranasal Sinuses / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism*; D012852:Sinusitis / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D018946:Chemokine CCL5; D015848:Interleukin-5; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor