Vaginal Response Research Articles

Sublingual immunization with an engineered Bacillus subtilis strain expressing tetanus toxin fragment C induces systemic and mucosal immune responses in piglets

Sublingual (SL) and intranasal (IN) administration of a Bacillus subtilis-based tetanus vaccine was tested in piglets, which more closely mimic the human immune system than mice. Piglets were immunized by the SL, IN or oral routes with vaccine expressing tetanus toxin fragment C, or commercial tetanus vaccine given by intramuscular injection as a control. Tetanus toxoid specific ELISA and passive neutralization tests were used to measure IgG and IgA levels in serum and mucosal secretions, and assess protective serum antibodies, respectively. The nature of the immune response was explored by MHC Class II, TGF-β1 expression, and ELISA assays for multiple cytokines. SL or IN immunization of piglets induced neutralizing tetanus toxoid specific serum antibody and local salivary and vaginal IgA responses. Standard tetanus vaccine resulted in systemic antibodies, whereas oral administration of the Bacillus-based vaccine was ineffective. Further analyses indicated a balanced Th1/Th2 response to SL or IN immunization. ConclusionThis study demonstrates for the first time that SL or IN administration is effective for inducing both systemic and mucosal responses in a piglet model, indicating that SL or IN delivery of a B. subtilis-based tetanus vaccine can be a simple, non-invasive, low cost strategy to induce immunity to tetanus.

Identification of Immune Cells by Flow Cytometry in Vaginal Lavages from Women with Vulvovaginitis and Normal Microflora

The extent of the vaginal immune response is not fully determined. The purpose of this study was to evaluate the vaginal immune cells from women with vulvovaginitis (VV). A total of 142 volunteers diagnosed with bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and BV associated with VC or normal microflora were sampled to evaluate the immune cells by flow cytometry. The immune cells were obtained by vaginal lavage and labeled with fluorochrome-conjugated monoclonal antibodies to identify neutrophil granulocytes, macrophages, CD4(+) and CD8(+) T lymphocytes, B lymphocytes, and NK lymphocytes. Neutrophil granulocytes were present in 84.6% of samples among the leukocyte populations. Considering samples in which neutrophils were present, the mean percentage of neutrophil granulocytes was significantly higher in women with VC than BV and normal microflora and was significantly lower in women with BV than normal microflora. Macrophages and lymphocytes were present in a lower percentage of samples. The mean percentage of CD4(+) T lymphocytes in vaginal lavages was significantly higher in VC and BV compared with women with normal microflora. Neutrophils were the predominant leukocytes and were associated with VC and inversely with BV. CD4(+) T lymphocytes were associated with both VC and BV.

Development of a self-contained, indwelling vaginal temperature probe for use in cattle research

A device was developed to monitor the vaginal temperature of cattle in a research setting. This device decreases labor involved with monitoring body temperature compared with manual temperature readings, allows for continuous monitoring of vaginal temperature at 1min intervals, and also allows for temperature measurements without the presence of a human handler or without restraint, which can agitate cattle. The device consists of a blank controlled internal drug release (CIDR) device (designed by Pfizer Animal Health as an indwelling vaginal probe) that holds an indwelling vaginal temperature probe logger. The fabrication of the vaginal probe costs approximately US $325 per unit. Similar rectal and vaginal temperature responses to lipopolysaccharide challenge were observed when vaginal and rectal temperatures were measured simultaneously in the same heifer (P>0.05). Additionally, rectal and vaginal temperatures were highly correlated (r=0.97; P<0.0001). Similar to the rectal temperature monitoring device, the vaginal device allows for the measurement of vaginal temperature without the potential biases associated with the stress response produced as a reaction to the handling by and (or) presence of humans. The vaginal temperature recording device will provide researchers with an additional inexpensive tool to study physiological responses in female cattle.

Antibacterial activity of a synthetic peptide that mimics the LPS binding domain of Indian mud crab, Scylla serrata Anti-lipopolysaccharide Factor (SsALF) also involved in the modulation of vaginal immune functions through NF-kB signaling

Recently the cDNA coding for anti-lipopolysaccharide factor (ALF) has been identified from the Indian mud crab, Scylla serrata and has been named S. serrata anti-lipopolysaccharide factor (SsALF). SsALF protein sequence demonstrated the presence of two highly conserved cystine residues between which the putative lipopolysaccharide (LPS) binding domain is known to be located. In this study, we have designed and synthesized a 24 amino acid linear (lSsALF24) and a cyclic (cSsALF24) peptides based on this putative LPS binding domain and demonstrated the ability of these peptides to bind to LPS. The peptides were active against vaginal pathogens demonstrated by MIC, CFU and phagocytosis assays. cSsALF24 did not show toxicity to human vaginal epithelial cells (HeLa-S3), macrophages and rabbit erythrocytes even at high concentration (64.64 μM). Flow cytometry results demonstrated that cSsALF24 peptide suppressed LPS induced phagocytosis of FITC labeled E. coli. HeLa cells were stimulated with LPS (10 μg/ml) alone for 6 h or after two washings with PBS, treated for 1 h with cSsALF24 (64.64 μM). After washing, the cells were cultured for 24 h in fresh media. The spent media as well as cells were collected for the determination of cytokine/chemokine levels such as interleukin-6 (IL-6) interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and interleukin-1α (IL-1α) using ELISA and RT-PCR respectively. Similar results were obtained with LPS stimulated cells treated with c/nSsALF24 or unstimulated cells treated with c/nSsALF24. The expression of cytokine/chemokines and mRNA’s coding these proteins were unaffected in c/nSsALF24 treated cells. In contrast, in LPS stimulated cells, the expression levels of these molecules were up-regulated via the induction of nuclear factor kappa-B (NF-kB) levels. However, the expression of these pro-inflammatory markers was decreased in LPS stimulated cells following the treatment with cSsALF24, attributing anti-inflammatory potential of the peptide. Collectively, these findings suggest that cSsALF24 might regulate the vaginal epithelial cell immune responses indirectly through modulation of LPS-TLR4 binding in NF-kB pathway.

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates.

The Sensitivity of Continuous Laboratory Measures of Physiological and Subjective Sexual Arousal for Diagnosing Women with Sexual Arousal Disorder

Past findings on the diagnostic sensitivity of vaginal photoplethysmography are limited by testing among women with heterogeneous sexual dysfunctions and by the use of statistical techniques that are unable to assess how changes in subjective arousal are associated with changes in physiological arousal. The aims of this study were to: (i) test the sensitivity of vaginal photoplethysmography and continuous measures of subjective sexual arousal in differentiating between women with and without sexual arousal or orgasm dysfunction; and (ii) examine the diagnostic utility of measuring the synchrony between genital and subjective sexual responses. Sexual arousal was assessed in sexually healthy women (n = 12), women with orgasm disorder (OD; n = 12), and 38 women who met the criteria for the three subcategories of sexual arousal dysfunction described by Basson et al. (i.e., genital sexual arousal disorder [GAD; n = 9], subjective sexual arousal disorder [SAD; n = 13], and combined genital and subjective arousal disorder [CAD; n = 16]). Physiological sexual arousal was assessed using vaginal photoplethysmography, and subjective sexual arousal was measured continuously and using a Likert-scale in response to sexual videos. Women with GAD showed the lowest and women with CAD showed the highest levels of vaginal pulse amplitude response to erotic stimuli. Women with sexual arousal disorder showed significantly lower levels of subjective sexual arousal to erotic stimuli than did sexually healthy women. Relations between subjective and physiological measures of sexual arousal were significantly weaker among women with sexual arousal disorder than sexually healthy women or women with OD. Preliminary support was provided for the diagnostic utility of measuring the synchrony between subjective and genital arousal in women with sexual arousal disorder. Findings do not support the sensitivity of using vaginal photoplethysmography, or continuous or Likert-scale measures of subjective arousal for differentiating between subtypes of women with sexual arousal disorder.

Targeting of whole killed bacteria to gastrointestinal M-cells induces humoral immunity in the female reproductive tract

Recently, we demonstrated that oral delivery of whole killed bacteria, when agglutinated by an M-cell targeting lectin, resulted in an enhanced systemic and mucosal antibody response, as well as a protective immunity, against the gut pathogens Helicobacter pylori and Campylobacter jejuni. Importantly, this protection was achieved without the addition of exogenous adjuvant. Here, in this addendum, we extend this initial study by reporting on the vaginal antibody response induced by these vaccinations. These data show that the targeting of M-cells within the gastrointestinal tract also induces the secretion of antigen-specific antibodies (IgG and IgA) at a distal mucosal site, namely the vaginal mucosa. This observation raises the possibility that oral delivery of a whole, killed bacteria vaccine that target intestinal M-cells could potentially provide a strategy for inducing protective immunity against pathogenic bacteria that infect mucosal sites outside the gastrointestinal tract.

Effects of Pregnancy and Bacterial Vaginosis on Proinflammatory Cytokine and Secretory Leukocyte Protease Inhibitor Concentrations in Vaginal Secretions

We compared vaginal proinflammatory cytokine and secretory leukocyte protease inhibitor (SLPI) concentrations among pregnant and nonpregnant women according to bacterial vaginosis (BV) status. One-hundred and twenty-two women at 12–20 weeks' gestation and 133 nonpregnant controls had vaginal concentrations of interleukin (IL)-1β, IL-6, IL-8, and SLPI measured by enzyme immunoassay. Multivariable linear regression was used to evaluate factors independently associated with vaginal cytokine and SLPI response. Pregnancy and BV were both independently associated with increased vaginal concentrations of IL-1β and IL-8; pregnant women had increased concentrations of SLPI, while women with BV had decreased SLPI concentrations.

Immunohistochemical study of the vaginal inflammatory response in experimental trichomoniasis

In the present paper, the acute and subchronical inflammatory processes of the vaginal epithelial were studied in mice experimentally infected with two Trichomonas vaginalis strains of different pathogenicity, by means of histological and immunological methods. There was an increase in the stratified epithelium layers as well as edema produced by the increase of vascularization in the propia submucosa and infiltration of leukocytes. The proliferation of the vaginal epithelium favors the settlement and persistence of the parasitic infection. All of the findings corresponded with signs of a systemic disease being observed in the animals, including significant weight loss and also intestinal invasion. The entire inflammatory process has been corroborated by studies of adhesion molecules such as E-Selectin, VCAM-1 and PECAM-1. A correlation between the time of appearance and the perseverance of the inflammatory process with E-Selectin and VCAM-1 expression was observed, but not with PECAM-1. The strain with a higher pathogenicity was able to invade deep vaginal tissues and thus, parasites could not be detected by vaginal washings. This may be an important cause of diagnosis and treatment failure. Also, by the different localization of trichomonads, it appeared that the battle between host and parasite took place in different areas dependent upon the characteristics of the strain.

Effective vaginal DNA delivery with high transfection efficiency is a good system for induction of higher local vaginal immune responses

Abstract Objectives To investigate the local vaginal and systemic immune responses of effective vaginal DNA delivery with high transfection efficiency, we determined the effects on Th1-dependent cytokine (interferon-γ) production in spleen and inguinal lymph node cells and antibody responses of vaginal pDNA immunization with a cell-penetrating peptide, and compared our vaginal immunization with intradermal and intranasal immunizations. Methods Mice were immunized by vaginal, nasal or dermal administration of pCMV-OVA with or without peptide carriers, and serum, vaginal fluids, spleen and inguinal cells were harvested. The serum immunoglobulin (Ig)G2a and vaginal IgA antibody responses were determined by sandwich enzyme-linked immunosorbent assay (ELISA). The interferon-γ production from spleen cells or inguinal lymph node cells was determined by an ELISA kit. Key findings The direct vaginal immunization strongly induced IgA in the vaginal fluids and interferon-γ production in the local lymph node draining from the vagina. In addition, co-vaccination with the peptide carriers elevated these immune responses compared with vaccination with pCMV-OVA alone. Vaginal immunization with high transfection efficiency promoted vaginal IgA production to a significantly greater extent than intradermal or nasal immunization. Conclusions These results suggested that direct vaginal DNA vaccines under high transfection conditions induced higher local vaginal antibody than that by intranasal or intradermal administration, and peptide carriers effectively elevated mucosal immune responses. Therefore, this vaginal DNA vaccination method may be expected to be useful in the prevention and treatment methods for vaginal infectious diseases such as HIV infection.

Effective vaginal DNA delivery with high transfection efficiency is a good system for induction of higher local vaginal immune responses

To investigate the local vaginal and systemic immune responses of effective vaginal DNA delivery with high transfection efficiency, we determined the effects on Th1-dependent cytokine (interferon-gamma) production in spleen and inguinal lymph node cells and antibody responses of vaginal pDNA immunization with a cell-penetrating peptide, and compared our vaginal immunization with intradermal and intranasal immunizations. Mice were immunized by vaginal, nasal or dermal administration of pCMV-OVA with or without peptide carriers, and serum, vaginal fluids, spleen and inguinal cells were harvested. The serum immunoglobulin (Ig)G(2a) and vaginal IgA antibody responses were determined by sandwich enzyme-linked immunosorbent assay (ELISA). The interferon-gamma production from spleen cells or inguinal lymph node cells was determined by an ELISA kit. The direct vaginal immunization strongly induced IgA in the vaginal fluids and interferon-gamma production in the local lymph node draining from the vagina. In addition, co-vaccination with the peptide carriers elevated these immune responses compared with vaccination with pCMV-OVA alone. Vaginal immunization with high transfection efficiency promoted vaginal IgA production to a significantly greater extent than intradermal or nasal immunization. These results suggested that direct vaginal DNA vaccines under high transfection conditions induced higher local vaginal antibody than that by intranasal or intradermal administration, and peptide carriers effectively elevated mucosal immune responses. Therefore, this vaginal DNA vaccination method may be expected to be useful in the prevention and treatment methods for vaginal infectious diseases such as HIV infection.

P11-09. Mucosal vaccination with a transferrin-gp140 conjugate via the nasal but not vaginal route elicits robust systemic and vaginal IgG and IgA responses

Background Mucosal anti-HIV immunity at the virus portal of entry is likely essential to protect against sexual transmission of HIV. While the female genital tract has some immuneinductive potential, responses elicited to vaccine antigens applied to the vaginal mucosae have been modest at best. Immunological linkage between nasal and vaginal MALT has been demonstrated in both mouse and man, suggesting that nasal vaccination may promote vaginal mucosal immunity. We used a novel transferrin receptor targeted vaccine conjugate to enhance delivery of a vaccinating antigen across the mucosal epithelial barrier and compared nasal with vaginal vaccination.

Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally

The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens (CE) cream for treatment of atrophic vaginitis. Postmenopausal women (N = 423) with moderate-to-severe vaginal atrophy were randomized to CE cream 0.3 mg or placebo once daily (21 days on/7 days off) or twice weekly for 12 weeks, followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen. Primary endpoints were changes in vaginal maturation index (VMI; percentage of superficial cells), vaginal pH, and severity of participant-reported most bothersome symptom (vaginal dryness, itching, burning, or dyspareunia) at week 12. Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks. At week 12, improvements in VMI with daily and twice-weekly use of low-dose CE cream (27.9% and 25.8%, respectively) were significantly greater compared with placebo (3.0% and 1.0%, respectively; P < 0.001). Improvements in vaginal pH with daily and twice-weekly CE cream (-1.6 for both) were also significantly greater relative to placebo (-0.4 and -0.3, respectively; P < 0.001). VMI and vaginal pH responses were sustained through 52 weeks. Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo (P < or = 0.001), including those for dyspareunia (P < or = 0.01). There was no report of endometrial hyperplasia or carcinoma. Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase. Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy. Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy.

Women’s health—what’s new worldwide

Women’s health—what’s new worldwide

Activation of Somatosensory Afferents Elicit Changes in Vaginal Blood Flow and the Urethrogenital Reflex Via Autonomic Efferents

We examined the effects of pudendal sensory nerve stimulation and urethral distention on vaginal blood flow and the urethrogenital reflex, and the relationship between somatic and autonomic pathways regulating sexual responses. Distention of the urethra and stimulation of the pudendal sensory nerve were used to evoke changes in vaginal blood flow (laser Doppler perfusion monitoring) and pudendal motor nerve activity in anesthetized, spinally transected female rats. Bilateral cuts of either the pelvic or hypogastric nerve or both autonomic nerves were made, and blood flow and pudendal nerve responses were reexamined. Stimulation of the pudendal sensory nerve or urethral distention elicited consistent increases in vaginal blood flow and rhythmic firing of the pudendal motor nerve. Bilateral cuts of the pelvic plus hypogastric nerves significantly reduced vaginal blood flow responses without altering pudendal motor nerve responses. Pelvic nerve cuts also significantly reduced vaginal blood flow responses. In contrast, hypogastric nerve cuts did not significantly change vaginal blood flow. Bilateral cuts of the pudendal sensory nerve blocked pudendal motor nerve responses but stimulation of the central end evoked vaginal blood flow and pudendal motor nerve responses. Stimulation of the sensory branch of the pudendal nerve elicits vasodilatation of the vagina. The likely mechanism is via activation of spinal pathways that in turn activate pelvic nerve efferents to produced changes in vaginal blood flow. Climatic-like responses (firing of the pudendal motor nerve) occur in response to stimulation of the pudendal sensory nerve and do not require intact pelvic or hypogastric nerves.

Vaginal maturation index self-sample collection in mid-life women

During menopause, the ratio of the three vaginal epithelial cell types (parabasal, intermediate, and superficial) changes. The proportion of these vaginal cell types is categorized by the vaginal maturation index (VMI). The VMI provides an objective assessment of vaginal hormone response as well as overall hormonal environment. The aim of this study was to determine the concordance of self- and physician-collected samples for VMI and evaluate participant preference for self-collection. Twenty women aged 42 to 67 years were enrolled. Each woman received instructions and self-collected a sample for VMI analysis from her posterior lateral vaginal walls. Next, she underwent a vaginal speculum examination for physician VMI sampling. Finally, she completed a survey regarding sampling preference, ease of self-sampling, and previous vaginal experience. Correlation between physician- and self-collected samples were calculated using Pearson's correlation coefficient and Cronbach's alpha. Participant characteristics, vaginal experiences, and sampling preferences were summarized using frequencies and measures of central tendencies. The relationships between preference for sampling method and previous vaginal experiences were examined using Fisher's exact test. Average age of the 20 participants was 52.2 years (range, 42-67 y). Women had a variety of previous vaginal experiences ranging from tampon use (100%) to previous vaginal self-swabbing (15%). Average self-collected VMI was 48.4 (range, 13.8-83.5) and physician-collected VMI was 49.9 (range, 20.5-83.5) with a correlation of 0.97 (P < 0. 001), alpha = 0.94. The majority of women preferred self-collection (80%) to physician collection, and there was no difference in preference based on previous vaginal experiences. Nineteen women (95%) found the self-collection to be very easy, and one found it to be somewhat easy. Women can reliably self-collect samples for VMI, and the majority of women in our study preferred self-collection to physician collection. Vaginal self-sampling allows this technique for measuring overall hormonal environment to be used in clinical and epidemiological research.

Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman

BackgroundVaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for post-menopausal hormone therapy (HT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology.MethodsWe analyzed 19 vaginal biopsies from human subjects pre and post 3-month 17β-estradiol treated by expression profiling. Data were compared to transcriptional profiling generated from vaginal samples obtained from ovariectomized rats treated with 17β-estradiol for 6 hrs, 3 days or 5 days. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene.ResultsA positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation.ConclusionAt the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.

Vaginal blood flow after radical hysterectomy with and without nerve sparing. A preliminary report

Radical hysterectomy with pelvic lymphadenectomy (RHL) for cervical cancer causes damage to the autonomic nerves, which are responsible for increased vaginal blood flow during sexual arousal. The aim of the study of which we now report preliminary data was to determine whether a nerve-sparing technique leads to an objectively less disturbed vaginal blood flow response during sexual stimulation. Photoplethysmographic assessment of vaginal pulse amplitude (VPA) during sexual stimulation by erotic films was performed. Subjective sexual arousal was assessed after each stimulus. Thirteen women after conventional RHL, 10 women after nerve-sparing RHL, and 14 healthy premenopausal women participated. Data were collected between January and August 2006. The main outcome measure was the logarithmically transformed mean VPA. To detect statistically significant differences in mean VPA levels between the three groups, a univariate analysis of variance was used. Mean VPA differed between the three groups (P= 0.014). The conventional group had a lower vaginal blood flow response than the control group (P= 0.016), which tended also to be lower than that of the nerve-sparing group (P= 0.097). These differences were critically dependent on baseline vaginal blood flow differences between the groups. The conventional group follows a vaginal blood flow pattern similar to postmenopausal women. Conventional RHL is associated with an overall disturbed vaginal blood flow response compared with healthy controls. Because it is not observed to the same extent after nerve-sparing RHL, it seems that the nerve-sparing technique leads to a better overall vaginal blood flow caused by less denervation of the vagina.

Intranasal immunization of young mice with a multigene HIV-1 vaccine in combination with the N3 adjuvant induces mucosal and systemic immune responses

One of the major challenges for the development of an HIV vaccine is to induce potent virus-specific immune responses at the mucosal surfaces where transmission of virus occurs. Intranasal delivery of classical vaccines has been shown to induce good mucosal antibody responses, but so far for genetic vaccines the success has been limited. This study shows that young individuals are sensitive to nasal immunization with a genetic vaccine delivered in a formulation of a lipid adjuvant, the Eurocine N3. Intranasal delivery of a multiclade/multigene HIV-1 genetic vaccine gave rise to vaginal and rectal IgA responses as well as systemic humoral and cellular responses. As electroporation might become the preferred means of delivering genetic vaccines for systemic HIV immunity, nasal delivery by droplet formulation in a lipid adjuvant might become a means of priming or boosting the mucosal immunity.

Evidence of a TH1-Shift of Local Vaginal Inflammatory Response During Bacterial Vaginosis

To determine the levels of pro-inflammatory and anti-inflammatory cytokines in the vagina of healthy women and in bacterial vaginosis (BV) patients. Interleukin (IL)-1alpha, 1beta, 5 and 10 were analyzed by ELISA in vaginal wash fluids from 50 non-pregnant patients with BV and 112 healthy women. Levels of IL-1beta were higher and those of IL-10 lower in BV-patients than in healthy women. There was a tendency towards higher levels of IL-1alpha in BV patients, but these data were not statistically significant. We found evidence for a shift towards a TH1-dominated vaginal cytokine profile in the pathogenesis of BV. Levels of a TH1-cytokine were elevated and those of a TH2-cytokine lowered in BV-patients as compared to healthy controls. This points to a vaginal TH1-response during BV and to the importance of cell-mediated immunity in local vaginal infections.