A psychoeducation program for stress management and psychosocial problems in multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) patients should cope effectively with problems of life and with problems originating from the disease. This is important because it affects the course of the disease, psychiatric morbidity, and quality of life. OBJECTIVE: This study was carried out as an intervention design with a control group to assess the effects of psychoeducation on MS patients' ways of coping with stress, psychiatric symptoms, and qualities of life. SUBJECTS AND METHODS: A total of 80 MS patients affiliated with the MS Association of Turkey were included and randomly assigned into intervention and control groups. An 8-week psychoeducation program was offered to the intervention group, whereas the control group was not given any treatment during the same period. Data were collected using a Descriptive Information Form, the Ways of Coping Inventory, the Brief Symptom Inventory, and the MS Quality of Life-54 scale. RESULTS: Based on the study, among the ways of coping with stress, problem-focused approach increased, whereas the emotional-focused approach decreased statistically significantly in the intervention group. Among the psychiatric symptoms, the levels of anxiety, depression, and somatization decreased. However, there was no significant change in the negative self-concept and hostility symptoms. The total quality-of-life scores increased significantly (P < 0.05). In the intervention group, these effects continued in the three-month-follow-up measurement. The control group showed no statistically significant change in the same parameters during the same periods. It is recommended that group psychoeducation programs should be carried out extensively in order for MS patients to cope with stress effectively and improve their mental health and quality of life.

Inflammatory 'double hit' model of temporomandibular joint disorder with elevated CCL2, CXCL9, CXCL10, RANTES and behavioural hypersensitivity in TNFR1/R2-/- mice.

BACKGROUND: Patients with temporomandibular joint disorders (TMD), reactive arthritis and rheumatoid arthritis often have combined etiology of hereditary and microenvironmental factors contributing to joint pain. Multiple clinical and animal studies indicate 'double-hit' inflammatory insults can cause chronic inflammation. The first inflammatory insult primes the immune system and subsequent insults elicit amplified responses. The present 'double hit' study produced a chronic orofacial pain model in mice with genetic deletion of both TNFα receptors (TNFR1/R2-/-), investigating the main nociceptive signalling pathways in comparisons to wild type mice. METHODS: An initial inflammatory insult was given unilaterally into the temporomandibular joint (TMJ). Secondary hypersensitivity was tested on the skin over the TMJ throughout the experiment. Three weeks later after complete reversal of hypersensitivity, a second inflammatory insult was imposed on the colon. Pharmacological interventions were tested for efficacy after week 10 when hypersensitivity was chronic in TNFR1/R2-/- mice. Serum cytokines were analysed at Days 1, 14, and Week 18. RESULTS: The double hit insult produced chronic hypersensitivity continuing through the 4-month experimental timeline in the absence of TNFα signalling. P2X7 and NMDA receptor antagonists temporarily attenuated chronic hypersensitivity. Serum cytokine/chemokine analysis on Day 14 when CFA induced hypersensitivity was resolved identified increased levels of pro-inflammatory cytokines CCL2, CXCL9, CXCL10, RANTES and decreased levels of anti-inflammatory cytokines IL-1ra and IL-4 in TNFR1/R2-/- compared to WT mice. CONCLUSIONS: These data suggest a causal feed-forward signalling cascade of these little studied cytokines have the potential to cause recrudescence in this orofacial inflammatory pain model in the absence of TNFα signalling. SIGNIFICANCE: Using a mouse model of chronic inflammatory temporomandibular joint disorder, we determined that absence of functional TNFR1/R2 induces aberrant inflammatory signalling caused by other increased pro-inflammatory and decreased anti-inflammatory cytokines that could serve as blood biomarkers and may predict disease progression.

CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense.

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases.

Dysregulated TNFα promotes cytokine proteome profile increases and bilateral orofacial hypersensitivity.

BACKGROUND: Tumor necrosis factor alpha (TNFα) is increased in patients with headache, neuropathic pain, periodontal and temporomandibular disease. This study and others have utilized TNF receptor 1/2 (TNFR1/2) knockout (KO) animals to investigate the effect of TNFα dysregulation in generation and maintenance of chronic neuropathic pain. The present study determined the impact of TNFα dysregulation in a trigeminal inflammatory compression (TIC) nerve injury model comparing wild-type (WT) and TNFR1/2 KO mice. METHODS: Chromic gut suture was inserted adjacent to the infraorbital nerve to induce the TIC model mechanical hypersensitivity. Cytokine proteome profiles demonstrated serology, and morphology explored microglial activation in trigeminal nucleus 10weeks post. RESULTS: TIC injury induced ipsilateral whisker pad mechanical allodynia persisting throughout the 10-week study in both TNFR1/2 KO and WT mice. Delayed mechanical allodynia developed on the contralateral whisker pad in TNFR1/2 KO mice but not in WT mice. Proteomic profiling 10weeks after chronic TIC injury revealed TNFα, interleukin-1alpha (IL-1α), interleukin-5 (IL-5), interleukin-23 (IL-23), macrophage inflammatory protein-1ß (MIP-1ß), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased more than 2-fold in TNFR1/2 KO mice compared to WT mice with TIC. Bilateral microglial activation in spinal trigeminal nucleus was detected only in TNFR1/2 KO mice. p38 mitogen-activated protein kinase (MAPK) inhibitor and microglial inhibitor minocycline reduced hypersensitivity. CONCLUSIONS: The results suggest the dysregulated serum cytokine proteome profile and bilateral spinal trigeminal nucleus microglial activation are contributory to the bilateral mechanical hypersensitization in this chronic trigeminal neuropathic pain model in the mice with TNFα dysregulation. Data support involvement of both neurogenic and humoral influences in chronic neuropathic pain.

An investigation of thermal comfort inside a bus during heating period within a climatic chamber.

By this study, it was aimed to define a testing and calculation model for thermal comfort assessment of a bus HVAC design and to compare effects of changing parameters on passenger's thermal comfort. For this purpose, a combined theoretical and experimental work during heating period inside a coach was carried out. The bus was left under 20 °C for more than 7 h within a climatic chamber and all heat sources were started at the beginning of a standard test. To investigate effects of fast transient conditions on passengers' physiology and thermal comfort, temperatures, air humidity and air velocities were measured. Human body was considered as one complete piece composed of core and skin compartments and the Transient Energy Balance Model developed by Gagge et al. in 1971 was used to calculate changes in thermal parameters between passenger bodies and bus interior environment. Depending on the given initial and environmental conditions, the graphs of passengers Thermal Sensation and Thermal Discomfort Level were found. At the end, a general mathematical model supported with a related experimental procedure was developed for the use of automotive HVAC engineers and scientists working on thermal comfort as a human dimension.

Effect of angiotensin II receptor blockers, candesartan, on osteoprotegerin level in hypertensive patients: Link between bone and RAAS.

INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS) has recently been considered as a possible link between bone and vascular disease. The present study was designed to determine the effect of the angiotensin II receptor blocker candesartan on circulating osteoprotegerin (OPG) in hypertensive patients with multiple cardiovascular risk factors. MATERIAL AND METHODS: A total of 69 hypertensive patients were randomized to two groups: Group 1 included patients treated with oral candesartan in doses of 16 mg to 32 mg per day in addition to routine standard of care (routine care + ARB), and Group 2 included patients who received routine standard of care other than ARBs or ACEIs, with no change to their treatment (routine care). Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, CRP, aldosterone, renin, homeostasis model assessment-insulin resistance (HOMA-IR) and OPG. RESULTS: Baseline OPG levels did not differ significantly by treatment group. Post-treatment serum OPG levels were marginally lower in Group1 compared with Group 2; however, this decrease did not reach statistical significance (p = 0.077). CONCLUSIONS: In the present study, treatment with the ARB candesartan had no significant effect on circulating OPG levels in hypertensive patients with multiple cardiovascular risk factors. To the best of our knowledge, the present study is the first to estimate an effect of candesartan on bone remodeling marker such as OPG.

A novel murine model for chronic inflammatory alveolar bone loss.

BACKGROUND AND OBJECTIVE: Chronic inflammatory bowel disease (IBD) demonstrates some similarities to the dysregulated chronic immunoinflammatory lesion of periodontitis. Trinitrobenzene sulphonic acid (TNBS) and dextran sodium sulphate (DSS) administered to rodents have been shown to elicit inflammatory responses that undermine the integrity of the gut epithelium in a similar manner to IBD in humans. The objective of this study was to evaluate the ability of these chemicals to elicit periodontal inflammation as a novel model for alveolar bone loss. MATERIAL AND METHODS: Mice were treated by oral application of TNBS twice a week, or with DSS in the diet over a period of 18 weeks. Alveolar bone loss was assessed on the defleshed skull using morphometric measures for area of bone resorption. RESULTS: The TNBS-treated animals tolerated oral administration with no clinical symptoms and gained weight at a similar rate to normal control animals. In contrast, DSS exerted a systemic response, including shortening of colonic tissue and liver enzyme changes. Both TNBS and DSS caused a localized action on periodontal tissues, with alveolar bone loss observed in both maxilla and mandibles, with progression in a time-dependent manner. Bone loss was detected as early as week 7, with more severe periodontitis increasing over the 18 weeks (p < 0.001). Young (7-month-old) and old (12-month-old) mice with severe combined immunodeficiency were treated with TNBS for a period of 7 weeks and did not develop significant bone loss. CONCLUSION: These data show that oral administration of TNBS or DSS provokes alveolar bone loss in concert with the autochthonous oral microbiota.

Mass absorption and mass energy transfer coefficients for 0.4-10 MeV gamma rays in elemental solids and gases.

The mass energy absorption, the mass energy transfer and mass absorption coefficients have been widely used for problems and applications involving dose calculations. Direct measurements of the coefficients are difficult, and theoretical computations are usually employed. In this paper, analytical equations are presented for determining the mass energy transfer and mass absorption coefficients for gamma rays with an incident energy range between 0.4 and 10 MeV in nitrogen, silicon, carbon, copper and sodium iodide. The mass absorption and mass energy transfer coefficients for gamma rays were calculated, and the results obtained were compared with the values reported in the literature.

Herpes in the peripartum period: a case report.

BACKGROUND: Despite the tremendous advances made in the management of genital herpes, neonatal herpes has not been completely eradicated. In addition, the time from the onset of symptoms in the neonate to the diagnosis of herpes and institution of antiviral medication has remained unchanged in the past 20 years. CASE: Neonatal herpes infection resulted from primary, first-episode peripartum genital herpes in the mother. Due to a high index of suspicion, herpes testing was performed on the infant and neonatal herpes diagnosed. Subsequently, the mother developed evidence of primary herpes infection. CONCLUSION: This case report illustrates the problems with current management strategies for prevention of neonatal herpes.

Percutaneous dilatational tracheostomy.

BACKGROUND: The aim of this study was to investigate the rate, timing, the incidence of complications of percutaneous dilatational tracheostomy (PDT) and its effects by on nosocomial pneumonia. METHODS: The study is a retrospective analysis of 104 patients (56 males, 48 females) > or = 18 years (54 +/- 19) who had undergone a PDT for respiratory failure during the five years 1998-2003. RESULTS: Among 238 patients requiring mechanical ventilation > or = 48 hours, 104 (43.7%) required PDT. PDT was performed after 4.3 +/- 2.3 days of ventilation and the disconnection from mechanical ventilation was 13.6 +/- 8.5 days. Lower airway tract infection was detected in 88 patients: 55 patients (62.5%) before PDT and in 33 patients (37.5%) after PDT. The nosocomial pneumonia was observed after 5.9 +/- 1.67 days of ventilation. CONCLUSIONS: Our results suggest that PDT was performed relatively early, with an acceptable complication rate and that our post-PDT nosocomial pneumonia incidence is low.

Effects of sevoflurane and desflurane on cytokine response during tympanoplasty surgery.

BACKGROUND: This study was devised to compare the effects of sevoflurane and desflurane anaesthesia on the cytokine response. METHODS: Sixty ASA I-II patients, scheduled for tympanoplasty, were randomly allocated to be anaesthetized with either sevoflurane or desflurane at maintenance inspiratory concentrations of 1-1.5 MAC of either agent. Blood samples were taken for plasma tumour necrosis factor alpha (TNFalpha), interleukin 1beta and interleukin-6 assay before induction of anaesthesia, before surgery, and at the end of surgery. Alveolar cells were obtained after induction of anaesthesia and at the end of surgery. RESULTS: Plasma TNFalpha was greater with desflurane than sevoflurane both before surgery (45.1 +/- 3.5 pg ml(-1) for desflurane vs. 23.2 +/- 2.5 pg ml(-1) for sevoflurane, P < 0.01) and (62.0 +/- 5.3 pg ml(-1) vs. 35.5 +/- 4.6 pg ml(-1), P < 0.001). Interleukin 1beta was similarly greater with desflurane than sevoflurane before (39.3 +/- 4.0 pg ml(-1) vs. 17.4 +/- 3.0 pg ml(-1); P < 0.01) and after surgery (46.0 +/- 3.4 pg ml(-1) vs. 23.3 +/- 3.2 pg ml(-1), P < 0.001). There were similar results for interleukin 6 before (42.3 +/- 3.5 pg mls(-1). 29.0 +/- 2.6 pg ml(-1), P < 0.001) and after surgery (86.0 +/- 4.5 pg ml(-1) vs. 45.9 +/- 6.3 pg ml(-1), P < 0.001). Alveolar cell TNFalpha concentrations after surgery were also greater with desflurane than sevoflurane (96.3 +/- 12.4 pg ml(-1) vs. 64.8 +/- 10.1 pg ml(-1), P < 0.001), as were interleukin 1beta (75.4 +/- 6.2 pg ml(-1) vs. 32.0 +/- 8.3 pg ml(-1), P < 0.001) and interleukin 6 concentrations (540.1 +/- 65.3 pg ml(-1) vs. 363.6 +/- 29.2 pg ml(-1), P < 0.001). CONCLUSION: Desflurane appears to cause a greater systemic and intrapulmonary pro-inflammatory response than sevoflurane during anaesthesia for ear surgery.

A simple system for producing, recording and broadcasting lectures and presentations.

Taking lecture notes has been the traditional starting point for revision; but in a high-tech age why miss important points whilst attempting to slowly transcribe a lecture, when we have the means to record it? This report aims to summarize information that may be used by anyone to provide good-quality, cost-effective provision of information via multimedia online lecture-materials. By applying and teaching simple techniques we can all ensure that each faculty and its students are exposed to the best of the wide world of online education, training and success.

Correlation of plasma and tissue oxidative stresses in intra-abdominal sepsis.

BACKGROUND: The aim of this study was to investigate the correlation between plasma and tissue oxidative stress and the antioxidative response, by measuring malon dialdehyde (MDA) and glutathione (GSH) in late sepsis induced by cecal ligation and perforation. MATERIALS AND METHODS: A prospective, randomized, controlled experimental study in rats was done. Forty rats, weighing 200-250 g, were randomly divided into two groups (n = 20). In group 1, laparotomy was performed under aseptic conditions, and the cecum ligated and perforated. The abdomen was closed. In group 2, sham control, there was only laparotomy. Twenty-four hours later, blood samples were taken by cardiac puncture for plasma MDA and GSH, followed by harvesting of samples from lung, liver, kidney, and heart in both groups. RESULTS: In the liver, lung, plasma, heart, and kidney, MDA concentrations were increased in the sepsis group after 24 h (P < 0.001 for all organ samples). In the same organs, GSH concentrations were decreased by sepsis (P < 0.001 for all organ samples). In both groups, plasma MDA was positively correlated to MDA in heart (r = 0.82, P < 0.001), liver (r = 0.76, P < 0.001), lung (r = 0.78, P < 0.001), and kidney (r = 0.73, P < 0.001). Similarly, plasma GSH was positively correlated to GSH in liver (r = 0.93, P < 0.001), heart (r = 0.86, P < 0.001), lung (r = 0.91, P < 0.001), and kidney (r = 0.79, P < 0.001). CONCLUSIONS: Plasma MDA and GSH were positively correlated with tissue MDA and GSH in intra-abdominal sepsis in a rat model.

The effects of sevoflurane and desflurane on lipid peroxidation during laparoscopic cholecystectomy.

BACKGROUND AND OBJECTIVE: To compare the effects of sevoflurane and desflurane anaesthesia on lipid peroxidation. METHODS: We studied 40 healthy patients undergoing elective laparoscopic cholecystectomy. Patients were randomly allocated to be anaesthetized either with sevoflurane (n = 20) or desflurane (n = 20). Anaesthesia was maintained with inspiratory concentrations of sevoflurane 1-1.5 MAC (n = 20) or desflurane (n = 20). Samples were taken for plasma malondialdehyde and superoxide dismutase assays before induction of anaesthesia, before skin incision and at the end of surgery. Alveolar cell samples were obtained from the lungs using the technique of protective blind bronchoalveolar lavage, after induction of anaesthesia and at the end of surgery for malondialdehyde and superoxide dismutase concentrations. RESULTS: Plasma malondialdehyde increased more after the administration of desflurane than after sevoflurane: after induction 5.9 +/- 0.6 nmol mL(-1) for desflurane vs. 3.8 +/- 0.5 nmol L(-1) for sevoflurane (P < 0.001); at the end of the surgery: 6.7 +/- 0.4 nmol mL(-1) for desflurane vs. 4.2 +/- 0.3 nmol mL(-1) for sevoflurane (P < 0.001). There was a small but significant increase in plasma superoxide dismutase concentration after desflurane--from 24.2 +/- 1.2 to 24.9 +/- 0.9 U mL(-1) after induction and 25 +/- 1 U mL(-1) at the end of the surgery (P < 0.01)--but no increase with sevoflurane. Malondialdehyde concentrations increased significantly in the cells obtained by protective blind bronchoalveolar lavage at the end of surgery in the desflurane group (from 0.3 +/- 0.1 to 1.7 +/- 0.2 nmol mL(-1) (P < 0.001)), but not in the sevoflurane group. There were no significant differences between the two anaesthetics in the amounts of superoxide dismutase in the samples obtained by protective blind bronchoalveolar lavage. CONCLUSIONS: Desflurane may cause more systemic and regional lipid peroxidation than sevoflurane during laparoscopic cholecystectomy in healthy human beings.

The green tea polyphenol (-)-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6.

The I kappa B kinase complex (IKK) mediates activation of the transcription factor nuclear factor-kappa B (NF-kappa B). We previously showed that green tea polyphenols inhibited endotoxin-mediated tumor necrosis factor-alpha (TNF alpha) production by blocking NF-kappa B activation. In this study, we evaluated whether green tea polyphenols inhibit NF-kappa B by blocking IKK activity. We assessed IKK activity by detecting changes in phosphorylation of an I kappa B alpha-glutathione S-transferase (GST) fusion protein. IEC-6 cells pretreated with an extract of green tea polyphenols (GrTPs; 0--0.4 mg/ml) had diminished TNF alpha-induced IKK and NF-kappa B activity. Of the various GrTPs, (-)-epigallocatechin-3-gallate (EGCG) was the most potent inhibitor. We next examined whether EGCG inhibited activated IKK. In cytosolic extracts of TNF alpha-stimulated cells, EGCG inhibited phosphorylation of I kappa B alpha-GST (IC(50) > 18 microM) consistent with inhibition of IKK activity. Using other polyphenols, we showed that the gallate group was essential for inhibition, and antioxidants were ineffective in blocking activated IKK. Importantly, EGCG decreased IKK activity in cytosolic extracts of NIK transiently transfected cells. This latter finding showed that our findings were not related to nonspecific kinase activity. In conclusion, EGCG is an effective inhibitor of IKK activity. This may explain, at least in part, some of the reported anti-inflammatory and anticancer effects of green tea.

Green tea polyphenol extract attenuates inflammation in interleukin-2-deficient mice, a model of autoimmunity.

Green tea polyphenols (GrTP) have been previously shown to decrease endotoxin-induced tumor necrosis factor-alpha production and lethality in mice. Our present studies demonstrate that GrTP inhibit inflammatory responses and may be useful in treating chronic inflammatory states, such as inflammatory bowel disease. In this preliminary study, we examined whether GrTP decrease disease activity in interleukin-2-deficient (IL-2(-/-) mice. Eight-week old IL-2(-/-) C57BL/6J mice who were fed nonpurified diet were randomly assigned to receive water with GrTP (5 g/L) or water alone (control) for up to 6 wk. After 1 wk, explant colon and lamina propria lymphocyte (LPL) cultures were established from a subgroup of mice and supernatants collected. Culture supernatants from GrTP-treated mice showed decreased spontaneous interferon-gamma and tumor necrosis factor-alpha secretion compared with that of controls. At 6 wk, the GrTP group had less severe colitis as demonstrated by lower histologic scores and wet colon weights. This was associated with lower plasma levels of serum amyloid A, increased weight gain and improved hematocrits. These results show that GrTP attenuated inflammation in IL-2(-/-) mice and suggest a role for GrTP in treating chronic inflammatory diseases such as inflammatory bowel disease.

Combination of granulocyte colony-stimulating factor and antibacterial drugs for the treatment of ventilatory associated nosocomial pneumonia.

In this prospective study, we aimed to investigate the role of Granulocyte Colony-Stimulating Factor (rhG-CSF) supplement to antibiotherapy, for the treatment of ventilator-associated nosocomial pneumonia (VAP) in patients intubated due to acute respiratory failure. In Emergency Intensive Care Unit (EICU), 28 patients on mechanical ventilation are randomised into two groups as rhG-CSF and control, after they are diagnosed to have VAP. The first group received 5 micrograms/kg/day subcutaneous rhG-CSF as a supplement to antibiotherapy while in the second group the sole treatment was antibiotherapy. For each patient studied, the chart is reviewed at the first day of mechanical ventilation and for 8 days after VAP for the following parameters: erythrocyte, leucocyte, granulocyte and platelet counts; SGOT, SGPT, blood urea, creatinine; microbiological analyses of transtracheal aspirate, hemocultures and infiltrations shown on chest x-ray. APACHE II scores of patients are also recorded. Statistical comparisons among groups are performed with Mann-Whitney U test. The groups didn't differ significantly in erythrocyte, platelet counts and blood urea, creatinine, SGOT, SGPT (p > 0.05). The difference is found to be much more significant according to leucocyte and granulocyte counts in rhG-CSF group, when compared to control group (p < 0.001). We conclude, that combination of antibacterial agents and rhG-CSF may be beneficial for the treatment of VAP.

A rat model for combined Trypanosoma cruzi and Pneumocystis carinii infection.

Dexamethasone treated rats inoculated with Trypanosoma cruzi developed acute parasitemia. In addition, these animals concomitantly developed severe Pneumocystis carinii pneumonia (PCP) and died after 4 weeks of immunosuppression (100%). However, immunocompetent (untreated) rats inoculated with T. cruzi did not acquire P. carinii and recovered from T. cruzi infection. Rats immunosuppressed, but not inoculated with T. cruzi, developed only PCP and died 5-6 weeks later (93%). In contrast, immunocompetent or immunocompromised IRC mice infected with T. cruzi all died of acute parasitemia in only 8-12 days with no detectable PCP infection. In conclusion, rats immunosuppressed and T. cruzi inoculated can serve as a MOPPS model for a single drug evaluation. In addition, T. cruzi infection independently does not provoke P. carinii pneumonia in this model. Finally, patients with Chagas' disease treated with corticosteroids may be at risk for PCP and should be considered for chemoprophylaxis.

Effect of CD40 ligand and other immunomodulators on Pneumocystis carinii infection in rat model.

The corticosteroid-treated animal is well established as an experimental model for the study of Pneumocystis carinii pneumonitis (PCP). Latent or acquired infection with P. carinii in the murine lung progresses to fatal pneumonitis when the host is profoundly immunocompromized. In this study the effects of five immunomodulators; recombinant CD40 ligand (CD40L), bryostatin 1, recombinant FLT3 ligand (FLT3L), recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant interleukin-15 (IL-15) were investigated against PCP in a dexamethasone immunosuppressed Sprague-Dawley rat model. The majority of rats (70%) treated with CD40L at the onset of dexamethasone immunosuppression were protected against PCP. When CD40L was given after 10 days of immunosuppression, only 40% of the rats resolved the infection. However, 95% of the control animals developed PCP. Immunosuppressed rats treated with bryostatin 1, an immune activator had a partial (50%) protection against P. carinii infection. In contrast, daily administration of FLT3L, IL-15 or G-CSF provided no protection against P. carinii infection.