Salivary gland hypofunction induced by activation of innate immunity is dependent on type I interferon signaling

Background: Activation of innate immunity through polyinosinic:polycytidylic acid [poly(I:C)] causes acute salivary gland hypofunction. As a major consequence of poly(I:C) treatment is type I interferon (IFN) production, this study was undertaken to investigate their role in salivary gland dysfunction. Methods: Different strains of mice deficient in either interferon alpha receptor (IFNAR1^?/?) or IL‐6^?/?, or IL‐10^?/?, or EBI3^?/? were treated with poly(I:C). Salivary gland function was determined by measuring pilocarpine‐induced saliva volume. Gene expression levels were measured by real‐time PCR. Ca²⁺ mobilization studies were performed using ex‐vivo acinar cells. Results: A single injection of poly(I:C) rapidly induced salivary gland hypofunction in wild‐type B6 mice (41% drop in saliva volumes compared to PBS‐treated mice). In contrast, the loss of function in poly(I:C)‐treated IFNAR^?/? mice was only 9.6%. Gene expression analysis showed reduced levels of Il‐6, Il‐10, and Il‐27 in submandibular glands of poly(I:C)‐treated IFNAR^?/? mice. While salivary gland dysfunction in poly(I:C)‐treated IL‐10^?/? and EBI3^?/? mice was comparable to wild‐type mice, the IL‐6^?/? mice were more resistant, with only a 21% drop in function. Pilocarpine‐induced Ca²⁺ flux was significantly suppressed in acinar cells obtained from poly(I:C)‐treated wild‐type mice. Conclusions: Our data demonstrate that a combined action of type I IFNs and IL‐6 contributes toward salivary gland hypofunction. This happens through interference with Ca²⁺ mobilization within acinar cells. Thus, in acute viral infections and diseases like Sjögren’s syndrome, elevated levels of type I IFNs and IL‐6 can directly affect glandular function.     

Expression of two drug-metabolizing cytochrome P450-enzymes in human salivary glands

Objective:  The oral cavity is constantly lubricated by saliva and even small amounts of xenobiotics and / or their metabolites in the saliva may affect the oral mucosa. Our aim was therefore to clarify if xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 are expressed in salivary glands.
Methods:  Formalin-fixed paraffin-embedded specimens from parotid (10), submandibular (7) and labial (10) salivary glands were examined immunohistochemically and by in situ hybridization for expression of CYP1A2 and CYP3A4 protein and mRNA.
Results:  CYP1A2 and CYP3A4 protein and mRNA were detected in ductal and seromucous / serous acinar cells in all gland types although to a varying degree and intensity. Mucous acinar cells were positive to a lesser extent.
Conclusion:  The results indicate a xenobiotic metabolizing capability of salivary glands. This may have implications for development of oral mucosal disease as a result of mucosal exposure to metabolites originating from internal sources (blood) as well as from saliva.     

Activation of innate immunity accelerates sialoadenitis in a mouse model for Sjögren's syndrome-like disease

Oral Diseases (2011) 17 , 801–807 Objective: Sjögren’s syndrome is a chronic autoimmune disorder characterized by progressive lymphocytic infiltration within the salivary and lacrimal glands. This study was undertaken to investigate the effects of innate immunity activation on sialoadenitis in a mouse strain genetically susceptible for development of SS‐like disease. Methods: Female New Zealand Black X New Zealand White F1 mice were repeatedly treated with toll‐like 3 receptor agonist poly(I:C). Submandibular glands were investigated at different time points for sialoadenitis by immunohistochemistry and for gene expression of different chemokines by quantitative PCR. Submandibular gland–infiltrating cells were characterized by flow cytometry. Results: Poly(I:C) treatment significantly upregulated the expression of multiple chemokines within the submandibular glands. The severity and incidence of sialoadenitis was considerably higher in poly(I:C)‐treated mice. There was a preponderance of dendritic cells and NK cells in the initial inflammatory cell infiltrates, and these were followed by CD4+ T cells. Conclusions: Our data clearly demonstrate that systemic activation of innate immunity accelerates sialoadenitis in a mouse model for SS‐like disease. These findings suggest that chronic activation of innate immunity can influence certain features of SS.     

Toll-like receptor activity in Recurrent Aphthous Ulceration

Background:  Toll-like receptors (TLR) are membrane proteins that recognize conserved molecules derived from bacterial, virus, fungal or host tissues. Activation of TLRs causes the production of cytokines that mediate inflammatory responses and drive T helper (Th) 1 and 2 cell development. As an exaggerated Th1 immune response is supposed to be involved in pathogenesis of Recurrent Aphthous Ulceration (RAU), we suggest that RAU patients may have an imbalance in TLR pathways.
Methods:  To study the function of TLR activation ex vivo , peripheral blood mononuclear cells (PBMCs) from RAU patients ( n  = 17) and controls ( n  = 17) were exposed to TLR2 [lipoteichoic acid (LTA), heat-killed Listeria monocytogenes (HKLM) and PamC3CSK4], TLR3 [Poly(I:C)], TLR4 [lipopolysaccharide (LPS)], TLR5 (flagellin) and TLR7 (imiquimod) ligands, and the time course of supernatant tumor necrosis factor-α (TNF-α) levels was quantified by enzyme-linked immunosorbent assay. In addition, serological and salivary TNF-α and soluble CD14 levels were quantified. The TNF-α produced by PBMCs in contact with each TLR ligand and autologous serum or saliva at the same time was also investigated. The data were analyzed by statistical multivariate tests.
Results:  The control group had a higher response to LTA, whereas RAU had a higher response to HKLM. LTA and LPS interfered with the salivary stimulation of the RAU PBMC and HKLM with the stimulation of the control. Autologous serum was capable of inhibiting TLR2 responsiveness to LTA and enhancing LPS stimulation. Salivary and serological levels of sCD14 and TNF-α were not significantly different.
Conclusion:  Recurrent Aphthous Ulceration patients have an anomalous activity of the TLR2 pathway that probably influences the stimulation of an abnormal Th1 immune response.     

Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation

Objective:  The commonly associated aetiology of salivary gland inflammation and salivary hypofunction has led to the widely held belief that inflammation causes salivary gland hypofunction. Indeed, our own recent study seemed to support this contention. Here, we tested the hypothesis that, in an acute duct ligation model, eliminating inflammation the submandibular gland would recover normal function.
Materials and methods:  Ligation of the rat submandibular gland excretory duct for 24 h was used to induce inflammation and salivary gland hypofunction. A group of duct ligated rats was compared with a second group given dexamethasone, on the day of duct ligation. Twenty-four hours later salivary gland function was assessed and salivary glands were collected.
Results:  Histology and myeloperoxidase activity assay revealed a profound decrease in inflammatory cell infiltration of ligated glands from rats given dexamethasone, compared with ligated glands in the absence of dexamethasone. Salivary flow rate evoked by methacholine was decreased ( P  < 0.01) by approximately 56% (ligated vs control, 79 ± 9  μ l min⁻¹ g⁻¹ vs 177 ± 11  μ l min⁻¹ g⁻¹) and salivary flow from ligated dexamethasone-treated and ligated glands was similar.
Conclusion:  Despite eliminating the inflammatory reaction in the ligated gland, salivary hypofunction was not reversed, suggesting that other mechanisms must be at work in the ligation-induced salivary hypofunction.     

The expression of the c-erbB-2 receptor protein in glandular salivary secretions

BACKGROUND: As the maintenance medium of the oral cavity, saliva is secreted from exocrine glands that include the parotid, submandibular, sublingual, and minor salivary glands. Considering that saliva is a fluid suffused with protein, it is possible that the solubilized by-products of oncogenic expression may be present in saliva. Recent studies suggest the presence of solubilized extracellular domain portion of the c-erbB-2 protein in serum, nipple aspirates, and saliva. As a consequence, the purpose of this study was to determine the presence and concentration of c-erbB-2 in major salivary gland secretions. METHODS: Fifteen healthy women had serum, stimulated whole (SWS), parotid (SP), and submandibular/sublingual (SS) salivary secretions collected. The specimens were analyzed for c-erbB-2 using enzyme linked immunosorbent assays (ELISAs). Western blots using c-erbB-2 were also performed on these specimens. RESULTS: The ELISAs revealed the presence of c-erbB-2 in SWS (24.50 Units/ml), SP (19.66 Units/ml), SS (15.59 Units/ml) and serum (1472.15 Units/ml). Western blots confirmed the presence of these 185 kDa proteins. CONCLUSIONS: These results suggest that the protein, c-erbB-2, is present in relatively equal amounts in both SP and SS glandular secretions. Elevated glandular salivary c-erbB-2 concentrations could be useful as a preliminary, non-invasive test in clinical decision making when diagnosing salivary gland carcinomas. Additionally, this marker may have utility in distinguishing between oral lesions that are benign, pre-malignant and malignant in the oral cavity. Further research is required to determine if these findings have clinical utility.     

Multiple components contribute to ability of saliva to inhibit influenza viruses

Introduction:  Saliva is a potentially important barrier against respiratory viral infection but its mechanism of action is not well studied.
Methods:  We tested the antiviral activities of whole saliva, specific salivary gland secretions, and purified salivary proteins against strains of influenza A virus (IAV) in vitro .
Results:  Whole saliva or parotid or submandibular/sublingual secretions from healthy donors inhibited IAV based on hemagglutination inhibition and neutralization assays. This differs from human immunodeficiency virus (HIV), for which only submandibular/sublingual secretions are reported to be inhibitory. Among purified salivary proteins, MUC5B, scavenger receptor cysteine-rich glycoprotein 340 (salivary gp-340), histatins, and human neutrophil defensins (HNPs) inhibited IAV at the concentrations present in whole saliva. In contrast, some abundant salivary proteins (acidic proline-rich proteins and amylase) had no activity, nor did several other less abundant salivary proteins with known activity against HIV (e.g. thrombospondin or serum leukocyte protease inhibitor). Whole saliva and MUC5B did not inhibit neuraminidase activity of IAV and viral neutralizing and aggregating activity of MUC5B was potentiated by the neuraminidase inhibitor oseltamivir. Hence, MUC5B inhibits IAV by presenting a sialic acid ligand for the viral hemagglutinin. The mechanism of action of histatins requires further study.
Conclusions:  These findings indicate that saliva represents an important initial barrier to IAV infection and underline the complexity of host defense activity of oral secretions. Of interest, antiviral activity of saliva against IAV and HIV differs in terms of specific glandular secretions and proteins that are inhibitory.     

Loss of PKCδ results in characteristics of Sjögren's syndrome including salivary gland dysfunction

Oral Diseases (2011) 17 , 601–609 Objectives: Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren’s Syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C‐delta (PKCδ) is known to play a critical role in B‐cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B‐cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ?/? mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined. Materials and methods: Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages. Results: PKCδ?/? mice have reduced salivary gland function, B220+ B‐cell infiltration, anti‐nuclear antibody production, and elevated IFN‐γ in the salivary glands as compared to PKCδ+//+ littermates. Conclusions: PKCδ?/? mice have exocrine gland tissue damage indicative of a SS–like phenotype.     

NOD mouse model for Sjögren's syndrome: lack of longitudinal stability

Objectives: The non‐obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjögren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno‐associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS‐like disease in NOD mice. Data collected over a 2‐year period indicated a changing SS phenotype in these mice and this phenomenon was investigated. Methods: 10¹⁰ particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared. Results: Salivary flow rate, focus score, and SMG cytokines interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, IL‐12(p70), tumor necrosis factor‐α and IFNγ showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non‐diabetic mice. Conclusion: This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice.     

A mouse model linking viral hepatitis and salivary gland dysfunction

Objective:  Viral hepatitis is known to cause xerostomia in humans, but this has not been reported in an animal model. We report a severe, acute, highly reproducible saliva deficiency occurring in BALB/c mice as a result of experimental viral hepatitis.
Materials and Methods:  BALB/c mice, splenectomized or carrying genetic mutations to detect immunological contributions to the saliva deficiency syndrome, were infected intraperitoneally with a non-lethal dose of murine cytomegalovirus. Pilocarpine-stimulated saliva volumes were determined between 0 and 15 days after infection. Salivary gland, liver, spleen, and sera were analyzed for the presence of virus, cytokines, inflammatory infiltrates, and tissue damage.
Results:  Saliva deficiency was detectable 2 days after cytomegalovirus infection, peaked at 88% below normal by day 7, and resolved partially in all mice by 15 days postinfection as sialoadenitis increased. Neither salivary gland viral titers, sialoadenitis, splenectomy, nor systemic inflammatory markers correlated with hyposalivation severity. Elevated liver enzymes did correlate with hyposalivation, and mice genetically resistant to murine cytomegalovirus-induced hepatitis were significantly protected.
Conclusions:  Murine cytomegalovirus-induced salivary gland dysfunction is biphasic, with an acute hepatitis-associated phase and a later sialoadenitis-associated phase. Acute murine cytomegalovirus infection of BALB/c mice may provide a model for investigation of hepatitis-associated xerostomia.     

Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS)

Objective:  To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS).
Design:  Longitudinal cohort study.
Subjects and methods:  A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands.
Main outcome measures:  Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no).
Results:  Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated ( P  =   0.01) and stimulated ( P  =   0.0004) salivary flow rates as well as salivary gland enlargement ( P  =   0.006) as compared with non-PI based HAART.
Conclusions:  PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.     

非肥胖型糖尿病小鼠唾液流率、颌下腺造影及病理研究

目的:研究非肥胖型糖尿病小鼠(nonobese diabetic mouse,NOD)唾液总流率;颌下腺造影及病理表现.材料及方法:本研究将56只NOD小鼠分9周、16周、20周及24周4个不同年龄组测定其唾液总流率,颌下腺造影及颌下腺病理学研究,用32只Balb/c小鼠分同样年龄组进行对照.结果:NOD小鼠唾液总流率随年龄增大而下降,Balb/c小鼠则变化不大.20周以后NOD小鼠颌下腺造影有造影剂外溢,排空功能明显迟缓.9周NOD小鼠颌下腺见淋巴细胞浸润,随年龄增长,淋巴细胞浸润加重.结论:NOD小鼠涎腺的形态及功能均明显受累,与人类SS表现类似.     

Transient TWEAK overexpression leads to a general salivary epithelial cell proliferation

Objectives:  Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that has pro-apoptotic, pro-angiogenic and pro-inflammatory effects. In liver, TWEAK leads to proliferation of progenitor oval cells, but not of mature hepatocytes. This study evaluated the hypothesis that TWEAK overexpression in salivary glands would lead to the proliferation of a salivary progenitor cell.
Methods:  A recombinant, serotype 5 adenoviral vector encoding human TWEAK, AdhTWEAK, was constructed, initially tested in vitro , and then administered to male Balb/c mice via cannulation of Wharton's duct. TWEAK expression in vivo was monitored as protein secreted into saliva and serum by enzyme-linked immunosorbent assays. Salivary cell proliferation was monitored by proliferating cell nuclear antigen staining and apoptosis was monitored using TUNEL staining.
Results:  AdhTWEAK administration led to a dose-dependent, transient TWEAK protein expression, detected primarily in saliva. Salivary epithelial cell proliferation was generalized, peaking on ∼days 2 and 3. TWEAK expression had no detectable effect on apoptosis of salivary epithelial cells.
Conclusion:  Transient overexpression of TWEAK in murine salivary glands leads to a general proliferation of epithelial cells vs a selective stimulation of a salivary progenitor cell.     

Immunochemical analysis of high molecular-weight human salivary mucins (MG1) using monoclonal antibodies

Using four Mabs with different specificities for salivary mucins, an ELISA has been developed in which human whole saliva, glandular salivas, salivary protein fractions and purified, high molecular-weight, mucin fractions (MG1) isolated from human submandibular and sublingual glandular tissues have been immunochemically analysed. All four Mabs reacted with MG1s. Three of them reacted with the purified, low molecular-weight salivary mucins (MG2). None was reactive with parotid saliva. MG1 preparations isolated from submandibular and sublingual glandular tissues of one and the same individual displayed different patterns of reactivity with these Mabs, indicating that they differ immunochemically. Analysis of the MG1s in salivas derived from individual salivary glands showed differences in immunochemical composition. These results indicate that the MG1 fraction in human whole saliva consists of several immunochemically different species.     

Cytokine concentrations in stimulated whole saliva among patients with primary Sjögren's syndrome, secondary Sjögren's syndrome, and patients with primary Sjögren's syndrome receiving varying doses of interferon for symptomatic treatment of the condition: a preliminary study

Sj?gren's syndrome is an autoimmune disorder which causes diminished salivary flow due to autoimmune sialoadenitis. This decrease in saliva flow is the result of inflammation and atrophy of the salivary glands. Most treatment regimens are palliative in nature, but treatment with interferon (IFN) holds promise for Sj?gren's syndrome sufferers. Several studies have investigated cytokine concentrations in the salivary glandular tissues from Sj?gren's syndrome patients; however, there is little information concerning cytokine expression in saliva. This is especially true with respect to treatment modalities and their effects on local cytokines. A clinical study was conducted to determine salivary interleukin (IL)-6, IFN, and IL-2, concentrations among subjects diagnosed with primary and secondary Sj?gren's syndrome and a healthy control group. The primary Sj?gren's syndrome showed significantly higher salivary IL-2 and salivary IL-6 than the control and secondary Sj?gren's groups. There were no between group differences for salivary IFN concentrations. In addition, the study assessed salivary IL-6, IFN, and IL-2 concentrations among 18 Sj?gren's syndrome patients before and after administration of IFN via the oral mucosal route. The results of the study showed that the mean values for the pre- and post-treatment groups for stimulated whole saliva flow rates were 3.15 and 3.74 ml/5 min, respectively. The post-treatment group exhibited a 16.8% increase in stimulated whole saliva flow rates. The salivary IL-6 concentration was 53.3% lower for the post-treatment group (17.79) as compared to the baseline value (33.35). The values for salivary IFN and salivary total protein were virtually unchanged from their baseline values. Salivary IL-2 values, however, were 50% lower in the post-treatment group (3.07) when compared to their respective baseline values (6.10). The results of this study suggest that healthy individuals exhibit lower salivary IL-2 and IL-6 as compared to individuals suffering from primary and secondary Sj?gren's syndrome. The results also suggest that administration of IFN via the oral mucosal route may increase salivary flow rates and depress certain cytokines (IL-2, IL-6) associated with inflammatory destruction of salivary glandular tissues in Sj?gren's syndrome patients.     

Simultaneous detection of IFN-gamma and IL-4 in lesional tissues and whole unstimulated saliva from patients with oral lichen planus

Background:  Although the roles of interferon (IFN)-gamma and interlekin (IL)-4 in oral lichen planus (OLP) have been described extensively in past decades, the available results are controversial. Moreover, few studies have utilized simultaneous detection of cytokines in local tissues and saliva to determine whether salivary cytokines could reflect the fact of local lesions.
Methods:  IFN-gamma and IL-4 were determined simultaneously in lesions and whole unstimulated saliva (WUS) from OLP patients with various clinical forms.
Results:  In OLP lesions, both IFN-gamma and IL-4 in erythematous/ulcerated OLP were higher significantly than that in control specimens. In WUS, however, only IFN-gamma of erythematous/ulcerated OLP was increased compared with control. Remarkably, IFN-gamma and IL-4 in WUS showed a more significant correlation to those in local tissues of all subjects.
Conclusion:  These results indicate that both IFN-gamma and IL-4 may play more important role in pathogenesis of erythematous/ulcerated OLP, and changes of these proinflammatory cytokines in WUS may reflect the status of the OLP lesion.     

Histamine deficiency inhibits lymphocyte infiltration in the submandibular gland of aged mice via increased anti-aging factor Klotho

ObjectivesHistidine decarboxylase (HDC), a histamine synthase, is expressed in various tissues and is induced by proinflammatory cytokines such as TNFα. As they age, C57BL/6 mice show auto-antibody deposition and lymphocyte infiltration into various tissues, including salivary glands. However, the mechanism underlying cell infiltration and the change in HDC expression in salivary glands with aging remain unclear. Thus, we aimed to elucidate the relationship between histamine and inflammaging.MethodsWe investigated the change in histology and HDC expression in the major salivary glands (parotid, submandibular, and sublingual) of 6-week- and 9-month-old wild-type mice. We also determined the histological changes, cytokine expression, and anti-aging factor Klotho in the salivary glands of 9-month-old wild-type and HDC-deficient (HDC-KO) mice.ResultsCell infiltration was observed in the submandibular gland of 9-month-old wild-type mice. Although most cells infiltrating the submandibular glands were CD3-positive and B220-positive lymphocytes, CD11c-positive and F4/80-positive monocyte lineages were also detected. HDC, TNFα, and IL-1β mRNA expression increased in the submandibular gland of 9-month-old wild-type mice. The expression of PPARγ, an anti-inflammatory protein, declined in 9-month-old wild-type mice, and Klotho expression increased in 9-month-old HDC-KO mice. Immunohistochemistry showed that Klotho-positive cells disappeared in the submandibular gland of 9-month-old wild-type mice, while Klotho was detected in all salivary glands in HDC-KO mice of the same age.ConclusionOur findings demonstrate the multifunctionality of histamine and can aid in the development of novel therapeutic methods for inflammatory diseases such as Sjogren's syndrome and age-related dysfunctions.     

Salivary secretion, mucin concentrations and candida carriage in HIV-infected patients

Objectives:  To test whether the submandibular/sublingual (SMSL) salivary secretion, mucin concentration and candida carriage status were altered in human immunodeficiency virus-positive (HIV+) patients.
Subjects and methods:  SMSL saliva collected from 48 HIV-infected and 31 HIV-negative men were analyzed for flow rates, total protein and mucin concentrations. Salivary cultures were performed for Candida assessment.
Results:  The salivary flow rate and protein secretion of the HIV+ patients was 37% and 32% less than that of the controls ( P  <   0.0001, P  =   0.0087). The mucin concentrations (MG1 and MG2) were higher in the HIV+ subjects compared with controls ( P  =   0.0186, P  =   0.0014); however, the mucin secretions were not different. The frequency of Candida -positive cultures was higher in the HIV+ subjects than in the controls (61.4% vs 24.1%, P  =   0.0018). In the HIV-infected group, the unstimulated SMSL flow rates were lower in Candida -positive than in Candida -negative patients ( P  =   0.0158).
Conclusion:  The salivary secretion of the SMSL glands was reduced in HIV infection. Although the mucin concentration increased in HIV+ subjects, mucin secretion was not altered. Highly active antiviral therapy had no effect on salivary function. We found an association between the level of candida carriage and salivary flow rate in HIV-infected patients.     

The relationship between the secretion of amylase and epidermal growth factor in the mouse submandibular salivary gland

Isoprenaline, a stimulant of exocrine secretion by the submandibular salivary glands of mice, does not produce depletion of the glandular epidermal growth factor. This supports the proposition that salivary glands in rodents may have an endocrine-like as well as an exocrine function.