Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck.

PURPOSE: There is a growing association of human papillomavirus (HPV) with some cases of mucosal squamous cell carcinoma of the head and neck (HNSCC), particularly of the oropharynx. Persistent oral HPV infection is believed to increase the likelihood of malignancy, and it is possible that host genetic factors can determine susceptibility to persistent HPV infection. Polymorphisms in the two EV genes (EVER1 and EVER2, also known as transmembrane channel protein (TMC) 6 and 8) have been identified as strong candidate genes, since a small number of critical mutations in these genes have been shown to cause profound and florid skin HPV infections, and some of them have been linked to susceptibility to cervical cancer. METHODS: We sought to determine whether there was a difference in the frequency of single nucleotide polymorphisms (SNPs) in EVER1 (rs2613516, rs12449858) and EVER2 (rs7205422, rs12452890) between HNSCC patients with HPV-positive and HPV-negative tumors, and healthy controls. We used logistic regression to analyze SNPs in 219 patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx, or larynx, and 321 healthy controls. RESULTS: We did not find any associations with the EVER1/EVER2 SNPs and HPV status or being a HNSCC case or a control. CONCLUSIONS: The present data do not provide evidence for a role of genetic variations in EVER1 or EVER2 for HPV status of mucosal HNSCC or between HNSCC patients and controls.

The burden of gastroesophageal reflux disease on the cost of managing chronic diseases in Australia. The need for a new diagnostic and management paradigm.

INTRODUCTION: Chronic disease poses a major problem for the Australian healthcare system as the leading cost-burden and cause of death. Gastroesophageal reflux disease (GORD) typifies the problems with a growing prevalence and cost. We hypothesise that a scintigraphic test could optimise the diagnosis, especially in problematic extraoesophageal disease. MATERIALS AND METHODS: Data was collected from 2 groups of patients. Patients undergoing fundoplication for severe GORD (n = 30) and those with atypical symptoms (n = 30) were studied by scintigraphy and 24-hour oesophageal pH, impedance and manometry. RESULTS: Mean age of cohort was 55.8 years with 40 females and 20 males. Body mass index was a mean of 28.3. DeMeester score was normal in 12/60 with atypical symptoms and abnormal in the rest. Good correlation was shown between scintigraphy and impedance, manometry and distal pH readings. Pulmonary aspiration was shown in 25/60 (15 with atypical symptoms) and LPR in 20/30. Several impedance, manometric and scintigraphic finding were good predictors of lung aspiration of refluxate. CONCLUSION: Scintigraphy provides a good tool for screening patients with typical and atypical symptoms of GORD. It is well correlated with the standard methods for the diagnosis and provides visual evidence of LPR and lung aspiration.

Novel approach to the formulation of an Epstein-Barr virus antigen-based nasopharyngeal carcinoma vaccine.

Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs.

Long-term functional speech and swallowing outcomes following pharyngolaryngectomy with free jejunal flap reconstruction.

Surgery for advanced cancer of the hypopharynx is a complex issue. Surgical intervention needs to take into consideration the resultant quality of life, in particular fundamental functional outcomes such as speech and swallowing. The aim of this study is to look at these long-term functional outcomes, following pharyngolaryngectomy and free jejunal reconstruction. A total of 19 patients, each undergoing a pharyngolaryngectomy with free jejunal graft was included. Each had a primary tracheoesophageal puncture for insertion of an indwelling voice prosthesis for speech. Functional outcomes of speech and swallow were assessed by a qualified speech pathologist. The impact on patients' quality of life was assessed under 4 domains: impairment, disability, handicap, and well being. The mean time period to follow-up was 4 years. Eighteen of the 19 patients were tolerating an oral diet, with one patient reliant on percutaneous endoscopic gastrostomy feeds. Seventeen patients (89%) were assessed as either having either no--or only a mild degree--of dysphagia, with no evidence of aspiration. Of the 19 patients, 15 were utilizing tracheosophageal speech for communication with 11 (73%) having no--or only a mild degree--of dsyphonia. Patients assessed as having no evidence of dysphagia or dysphonia also reported reduced levels of handicap and distress compared with patients experiencing any degree of dysphagia (P = 0.46) or dysphonia (P = 0.01). While rates of pharyngolaryngectomy increase, most patients have a poor long-term prognosis, heightening the significance of postoperative outcomes. The results of this study highlight the importance of speech and swallow outcomes, and demonstrate the direct correlation between these functions and resultant quality of life.

Optimization of LMP-specific CTL expansion for potential adoptive immunotherapy in NPC patients.

Nasopharyngeal carcinoma (NPC) is Epstein-Barr virus (EBV) positive in all undifferentiated cases, expressing the latency II phenotype of latent membrane proteins (LMPs) 1 and 2, in addition to EBV nuclear antigen (EBNA) 1. Several studies have attempted to treat NPC with EBV-specific cytotoxic T lymphocyte (CTL) with a partial response. To improve this therapy, there is a need to expand CTL targeted to the latency II antigens of EBV, rather than the immunodominant EBV nuclear antigens 3-6 peptides typically expanded by lymphoblastoid cells. In order to maximize the expansion of LMP-specific CTL in vitro for use in adoptive immunotherapy of nasopharyngeal carcinoma patients, we used lymphoblastoid cell lines coated with synthetic peptides corresponding to CTL determinants from the LMP proteins. We investigated several issues pertaining to the expansion of an immunologically weak CTL response, including peptide and interleukin-2 concentration, and screening assays for selecting the optimal peptide for use in expansion of LMP-specific CTL. Although screening of ex vivo peripheral blood mononuclear cells did not prove to be useful in the selection of an LMP peptide for use in CTL cultures, the peptide and interleukin-2 concentrations were critical for the maximum expansion of CTL. Therefore, it is imperative that stimulation protocols are optimized for the expansion of LMP-specific CTL.

Tonsillectomy in Australia: an audit of surgical technique and postoperative care.

OBJECTIVE: To assess current tonsillectomy practice among Australian otolaryngologists. STUDY DESIGN: An audit based on an anonymous 19-item postal questionnaire on tonsillectomy technique and perioperative management sent to all Australian otolaryngology specialists. SUBJECTS AND METHODS: Two hundred eighty-four otolaryngologists registered with the Australian Society of Otolaryngology-Head and Neck Surgery database were sent the questionnaire. RESULTS: A 72.5 percent response rate was obtained. Monopolar diathermy was the most common technique for dissection (45%) and hemostasis (54%). Bipolar diathermy was used for hemostasis in 20 percent. Cold-steel dissection was routinely used by 36 percent, ties were used for hemostasis only by 11 percent of surgeons. The use of local anesthetic, dexamethasone, and postoperative antibiotics was 45 percent, 40 percent, and 20 percent, respectively. Seventy-six percent of surgeons always observed tonsil patients overnight. CONCLUSION: Australian surgeons still use monopolar diathermy as their preferred technique for tonsillectomy. Local anesthetic, dexamethasone, and postoperative antibiotics are used infrequently, and fewer than 1:4 surgeons perform day-case tonsillectomy.

Locally advanced tonsillar squamous cell carcinoma: Treatment approach revisited.

AIMS: The purpose of this study was to review the treatment policy for locally advanced stage III and IV squamous cell carcinoma (SCC) of the tonsil at the Princess Alexandra Hospital Head and Neck Unit, Brisbane, Australia. MATERIALS AND METHODS: The records of 148 patients with curable stage III and IV SCC of the tonsil were reviewed from the years 1992 to 2004 inclusive. During this period, patients were treated with surgery and postoperative radiotherapy and only offered definitive radiation if they were medically or surgically inoperable. There were 102 patients treated with surgery +/- postoperative radiotherapy (group 1) and 46 patients treated with definitive radiotherapy +/- chemotherapy (group 2). The endpoints of locoregional control (LRC), disease specific survival (DSS), and overall survival (OS) were studied and prognostic factors were investigated with univariate and multivariate analyses. RESULTS: The 5-year OS, DSS, and LRC were 57%, 69%, and 84%, respectively. Univariate analyses showed that patients in group 1 had a superior OS (69% vs. 41%, P = .007), a trend toward improvement in LRC (88% vs. 73%, P = .08), and a nonsignificant improvement in DSS (75% vs. 56%, P = .14). There was a greater percentage of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 or less in group 1, suggesting selection bias toward the surgical group. Multivariate analyses, which adjusted for known prognostic factors, showed that treatment group was significant for OS but not for LRC or DSS. CONCLUSIONS: Surgery and postoperative radiotherapy continues to provide a superior outcome in locally advanced tonsil SCC in patients with surgically resectable disease, good ECOG performance status, and medically operable.

Squamous cell carcinoma of the floor of the mouth: tumour thickness and the rate of cervical metastasis.

BACKGROUND: Increased thickness of oral cavity squamous cell carcinoma (SCC) has been shown to be associated with higher rates of cervical metastasis. Most of the previous studies have focused on SCC of the oral tongue. There are few studies that have examined solely carcinoma of the floor of the mouth and these studies differ in the thickness of tumour that is associated with significantly increased rates of cervical metastasis. METHODS: Patients with SCC of the floor of the mouth of all stages who were treated with excision and neck dissection were identified. Primary tumour thickness and other pathological features were determined in the pathological specimens and were correlated to the incidence of pathological cervical lymph node metastasis. Fisher's exact test and the unpaired t-test were used for statistical analysis. RESULTS: Fifty-three patients were studied (43 men and 10 women). The median age was 56.5 years (range 43-86 years). The median tumour thickness in patients with lymph node metastases (14.6 mm) differed significantly from those without metastases (8.6 mm) (P = 0.004). When T1 and T2 cases were looked at in isolation, the median tumour thickness of cases with lymph node metastases (11.1 mm) again was significantly greater than those without metastases (4.6 mm) (P = 0.04). Subgrouping tumours into those > or =7.5 mm or < 7.5 mm showed a significantly increased rate of lymph node metastasis (57% compared with 12%, P = 0.001). There was no statistically significant association between perineural invasion or tumour differentiation and the presence of lymph node metastases. CONCLUSION: Tumour thickness has been shown to be directly related to rates of cervical lymph node metastasis in floor of mouth SCC. The primary tumour thickness associated with significantly increased rates of metastasis is similar to that shown in previous studies examining SCC of the oral tongue.

A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis.

OBJECTIVES: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. METHOD: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. RESULTS: There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P<.05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. CONCLUSION: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.

Alterations in gene expression and activity during squamous cell carcinoma development.

This study focuses on characterizing the genetic and biological alterations associated with squamous cell carcinoma development. Normal human epidermal keratinocytes (HEKs), cells isolated from a preneoplastic lesion (IEC-1), and two neoplastic cell lines, SCC-25 and COLO-16, were grown as raft cultures, and their gene expression profiles were screened using cDNA arrays. Our data indicated that the expression levels of at least 37 genes were significantly (P

Total pharyngolaryngectomy for squamous cell carcinoma of the hypopharynx: a review.

OBJECTIVES: To evaluate our experience with total pharyngolaryngectomy in the treatment of hypopharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective analysis of consecutively treated patients in an academic otolaryngology, head and neck department. METHODS: One hundred eighty patients who had total pharyngolaryngectomy performed for hypopharyngeal carcinoma were included in this study. Patients with a history of previous head and neck cancer were excluded. Clinicopathologic parameters were recorded and survival calculated using the Kaplan-Meier method. RESULTS: One hundred sixty-two (90%) of the patients were male, and the patients had a mean age of 62 years. The majority (91%) of patients had advanced overall clinical stage disease (stage 3,4). Thirty-one (17.8%) and 43 (24%) patients developed locoregional and metastatic disease recurrence, respectively. The 2- and 5-year disease-specific survival rates were 72% and 52%, respectively. Advanced nodal stage, perineural invasion, lymphovascular invasion, and positive margins were predictors of poor survival on univariate analysis, and lymphovascular invasion was an independent prognostic factor on multivariate analysis. CONCLUSION: Surgery and postoperative radiotherapy remains the treatment against which other modalities should be compared for advanced stage hypopharyngeal squamous cell carcinoma.

Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer.

OBJECTIVES: Gene expression profiling has provided many insights into tumor progression but translation to clinical practice has been limited. We have previously identified a list of potential markers by the differences of expression profiling of seven matched head and neck cancer (HNSCC) tumors with autologous normal oral mucosa (NOM). Alpha B-crystallin (CRYAB) was in the top 5% of genes identified with statistically significant differences in expression between tumor and NOM at the mRNA level. The objective was to confirm this in routine paraffin sections at the protein level. STUDY DESIGN: The level of alpha B-crystallin was determined in tumors of 62 HNSCC patients whose prognosis was known for 5 years. METHODS: Immunohistochemical detection of alpha B-crystallin expression was performed on HNSCC paraffin sections. RESULTS: Univariate survival analysis identified lack of alpha B-crystallin staining as an independent prognostic marker for disease-free interval (P < 0.001) and overall survival (P < 0.002) of HNSCC patients over the 5-year observation period. Notably, all 13 patients (100%), including 5 patients with nodal disease whose tumors lacked alpha B-crystallin had no recurrences (P < 0.001). Nineteen of 27 node-negative patients stained positive for alpha B-crystallin and seven of the 19 (36.8%) had recurrences. CONCLUSION: Presence or absence of expression of alpha B-crystallin was a powerful marker for prognosis in this series of patients.

Chemoprevention of head and neck cancer with retinoids: a negative result.

OBJECTIVE: To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to enter appropriate patients into this trial. PATIENTS: One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment. INTERVENTIONS: Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for 1 year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years. MAIN OUTCOME MEASURES: The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured. RESULTS: There was no significant difference in the occurrence of second primary disease (P = .90), the recurrence of primary disease (P = .70), or disease-free time (P = .80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival. CONCLUSION: With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.

Challenge-induced plasma exudation and mucinous secretion in human airways.

Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was exposed to increasing doses of histamine (40 and 400 microg ml(-1)), methacholine (12.5 and 25 mg) and capsaicin (30 and 300 ng ml(-1)). Fucose was selected as a global marker of mucinous secretion and alpha(2)-macroglobulin as an index of exudation of bulk plasma. All challenge agents increased the mucosal output of fucose to about the same level (P<0.01-0.05). Once significant secretion had been induced the subsequently increased dose of the challenge agent, in the case of histamine and methacholine, failed to further increase the response. Only histamine increased the mucosal output of alpha(2)-macroglobulin (P<0.01). We conclude that prompt but potentially rapidly depleted mucinous secretion is common to different kinds of airway challenges, whereas inflammatory histamine-type mediators are required to produce plasma exudation. Along with the acknowledged secretion of mucins, a practically non-depletable, pluripotent mucosal output of plasma emerges as an important component of the innate immunity of human airways.

First clinical experience with a new non-indwelling voice prosthesis (Provox NID) for voice rehabilitation after total laryngectomy.

CONCLUSION: The new Provox NID non-indwelling voice prosthesis investigated in this study provides a good option for laryngectomized patients using non-indwelling voice prostheses and can potentially improve safety and increase patients' satisfaction with their voice and speech. OBJECTIVE: To investigate the feasibility of and patient satisfaction with the Provox NID non-indwelling voice prosthesis. MATERIAL AND METHODS: Pre- and post-study questionnaires were used to evaluate the patients' former voice prosthesis and the Provox NID voice prosthesis. In addition, measurements of pull-out force, maximum phonation time and loudness were made for both voice prostheses. In vitro measurements of airflow characteristics were also made. Following a 6-week trial, all patients provided feedback on the new voice prosthesis and the results were used to further improve the Provox NID. This final version of the new voice prosthesis was subsequently trialled and evaluated by 10 patients 6 months later. RESULTS: Overall results showed that patient satisfaction with the Provox NID non-indwelling voice prosthesis was favourable. The pull-out force for the new prosthesis was significantly higher than that for the formerly used prosthesis and its aerodynamic characteristics were better.

Human papillomavirus status and p16(INK4A) expression in patients with mucosal squamous cell carcinoma of the head and neck in Queensland, Australia.

BACKGROUND: The last decade has seen changes in the epidemiology of mucosal squamous cell carcinomas of the head and neck (HNSCCs), with increasing numbers of cases attributable to human papillomavirus (HPV) infection. We sought to determine the prevalence of HPV and p16(INK4a) expression in Australian HNSCC patients and to identify predictors of HPV-positivity. METHODS: We recruited 248 HNSCC patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx diagnosed between 2004 and 2010. All patients completed a questionnaire. Clinical data were abstracted from medical records. HPV presence in paraffin-embedded tumours was determined by PCR, and expression of p16(INK4a), p21(WAF1), p53, pRB, cyclin D1, and Ki67 by immunohistochemistry. RESULTS: Fifty (20%) patients were HPV-positive, 63 (28%) overexpressed p16(INK4a), and 44 (19%) were positive for HPV and p16(INK4a) (high concordance between HPV-positivity and p16(INK4a) status, κ=0.72). HPV-16 was most common (84%), followed by HPV-18 (10%), HPV-33 (4%) and HPV-69 (2%). HPV and p16(INK4a) prevalence was highest for SCCs of the oropharynx, followed by hypopharynx, larynx and oral cavity (HPV and p16(INK4a)p<0.0001). HPV prevalence and p16(INK4a)-overexpression were significantly higher in younger than older patients (HPV p=0.001; p16 (INK4a)p=0.003). Heavy smokers had lower HPV prevalence than non- or moderate smokers (p=0.017). Gender and alcohol consumption were not associated with HPV or p16(INK4a) status. HPV-positive tumours had significantly lower cyclin D1 and higher p21(WAF1) expression than HPV-negative tumours. CONCLUSION: HPV prevalence and p16(INK4a)-overexpression were highest in oropharyngeal tumours, younger patients, and non-smokers.

Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis.

OBJECTIVES: Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. It is believed that macrolide antibiotics produce this benefit through an anti-inflammatory effect. In this study, the effect of clarithromycin treatment on the expression of transforming growth factor (TGF)-beta and the key pro-inflammatory nuclear transcription factor, NF-kappa B, was examined in vitro and in vivo. STUDY DESIGN AND METHODS: In vitro: nasal mucosa was obtained from 10 patients with chronic sinusitis and was cultured for 24 hours in the presence of clarithromycin or control. Cellular expression of TGF-beta and NF-kappa B was determined by immunohistochemistry. In vivo: 10 patients with chronic rhinosinusitis were treated for 3 months with clarithromycin. Nasal mucosal biopsies were taken pre- and posttreatment. Cellular expression of TGF-beta and NF-kappa B was again determined by immunohistochemistry. RESULTS: Clarithromycin, when applied to nasal biopsies in vitro, reduced cellular expression of TGF-beta and NF-kappa B. Nasal biopsies taken before and after clarithromycin treatment showed no differences in cellular expression of NF-kappa B or TGF-beta. CONCLUSION: Clarithromycin can reduce cellular expression of TGF-beta and NF-kappa B when applied in vitro, but its action during clinical therapy is less clear. Clarithromycin is capable of inhibiting pro-inflammatory cytokines in vitro, and reductions of TGF-beta and NF-kappa B may represent additional mechanisms by which macrolides reduce inflammation in chronic airway disease. Discrepancies between the actions of clarithromycin on nasal biopsies in vitro and after clinical therapy warrant further investigation.

Clarithromycin and prednisolone inhibit cytokine production in chronic rhinosinusitis.

OBJECTIVES: Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. The mechanism of its anti-inflammatory effect and how this differs from corticosteroids remains unclear. The effect of clarithromycin and prednisolone on interleukin-5, interleukin-8, and granulocyte-macrophage colony-stimulating factor production by cultured chronic sinusitis nasal mucosa was examined in the study. STUDY DESIGN AND METHODS: Nasal mucosa was obtained from 11 patients with chronic sinusitis. This tissue was cultured for 24 hours in the presence of clarithromycin or prednisolone at a variety of concentrations. Cytokine levels were determined by enzyme-linked immunoassay. RESULTS: Clarithromycin and prednisolone each produced significant reductions in interleukin-5, interleukin-8, and granulocyte-macrophage colony-stimulating factor production. There was no significant difference between the effects of clarithromycin and prednisolone. CONCLUSION: Macrolide antibiotics are capable of inhibiting pro-inflammatory cytokine production in vitro and are as potent as prednisolone. This mechanism is likely to be at least partly responsible for the clinical efficacy of macrolide antibiotics in chronic rhinosinusitis.