Differential chemokine expression patterns in tonsillar disease

Mandapathil, M.; H.Beier, U.; Graefe, H.; Kröger, B.; Hedderich, J.; Maune, S.; Meyer, J. E

Waldeyer's tonsillar ring acts as the first line of immune defence against microbes, entering the body nasally or orally. Especially in children, the immunogenic properties of the palatine tonsils are of particular importance. Chemokines are small signalling proteins, whose expression in various tissues is variably regulated during immune responses as well as acute and chronic infection. Previous studies have suggested a functional role for chemokines in hepatitis, colitis, pancreatitis, asthma and various malignancies as well as acute and chronic infections of the upper aerodigestive tract [18] [19] [20] [21] [22] [23] . Most chemokines are only produced and secreted upon appropriate stimulation of cells by bacterial or viral products 24 . In cases of acute and chronically infected tonsils, accumulation of certain subsets of chemokines and neutrophilic dynamics has been observed 25 . IL-8 has been described to be very potent in neutrophil activation and migration 26 27 . Our data shows significant overexpression of IL-8 in chronic inflammatory tonsillar disease. Since IL-8 expression has been reported to be effectively stimulated by TNF-a und IL-1ß for neutrophil chemotaxis as well as activity, our data suggests that a Th1 response is predominatly involved in the pathogenesis of chronic tonsillitis. Both IL-8 and GRO-α are known to be synthesised by neutrophils and fibroblasts in response to various stimuli 28 29 . In vitro, IL-1β and TNF-α seem to be potent stimulators of chemokine production, whereas IFN-γ inhibits their production 18 . GRO-alpha is further produced by endothelial cells, fibroblasts and monocytes after stimulation with lipopolysaccharide, IL-1 or TNF-α in vitro. In addition, it induces neutrophil accumulation and chemotaxis 29 . In our data however, GRO-alpha was not significantly overexpressed in chronic tonsillar diseases. Tonsillar hyperplasia appears to be a result of increased proliferation of lymphoid tissue predominantly triggered by bacterial infections. Previously, tonsil size has been shown to be directly proportional to the mean bacterial load 30 . The kind of bacteria found in hyperplastic tonsils does not seem to greatly differ from those in recurrently active infected tonsils. However, Haemophilus infection, besides Staphylococcus aureus and Streptococcus pyogenes appears to be more common in tonsillar hyperplasia 30 . Our investigations demonstrate that hyperplastic tonsillitis is characterised by an acute inflammatory chemokine pattern as IL-8 expression on mRNA levels correlates with the presence of actively infected tissue. IL-8 expression was significantly elevated in acutely infected tissue compared to hyperplastic tonsils (p < 0.01), and in adenoids and chronic tonsillitis compared to hyperplastic tonsils (p < 0.05). Therefore, as IL-8 is an acute phase chemokine expressed in chronic tonsillitis, this suggests an inflammatory process in the pathogenesis of chronic tonsillitis. An elevation of IL-8 in acute infections has been described previously 31 32 , and therefore anticipated for tonsillar dis-ease. However there have been studies showing an equal expression of IL-8 in hyperplastic tonsils and chronic tonsillitis 33 . Another reason for a high expression of this chemokine in chronic and hyperplastic disease could be its additional extensive effect on cell proliferation 34 . A similar result would have been expected for the expression of GRO-alpha, since this chemokine also plays an important