BACKGROUND:Psoriasis is a systemic inflammatory disease with a pathophysiology involving interleukin (IL)-17. Tofacitinib is an oral Janus kinase inhibitor. Etanercept is a tumour necrosis factor-α inhibitor used in the treatment of psoriasis. Neither agent inhibits IL-17 directly.AIM:To evaluate correlations between circulating IL-17A and clinical efficacy in patients with psoriasis treated with tofacitinib or etanercept.METHODS:Serum concentrations of IL-17A homodimer and IL-17A/F heterodimer were determined by immunoassays at weeks 0, 4 and 12 in patients with moderate to severe psoriasis treated with placebo (n = 60), tofacitinib 5 mg twice daily (n = 184), tofacitinib 10 mg twice daily (n = 190), or etanercept 50 mg subcutaneously twice weekly (n = 190). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI) and clinical response was defined as patients achieving ≥ 75% improvement from baseline PASI (PASI75).RESULTS:Serum levels of IL-17A homodimer at week 0 showed moderate correlation with PASI, with a Spearman correlation coefficient of 0.43. Furthermore, serum levels of IL-17A homodimer showed a clear correlation with clinical response, with a decrease of 57.1% in patients achieving PASI75 at week 12, but only 15.9% decrease in nonresponders. PASI75 responders had lower median concentrations of IL-17A (range across treatments: 0.24-0.27 pg/mL) at week 12 vs. nonresponders (0.37-0.62 pg/mL), regardless of the treatment. Serum IL-17A/F heterodimer showed similar decreases at week 12 in responders and nonresponders.CONCLUSIONS:Baseline serum IL-17A correlates moderately with psoriasis severity. Reduction in circulating IL-17A is required for disease remission regardless of therapeutic agent.

High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative effect and enhanced local and systemic production of this cytokine after organ injuries. The possibility of using serial serum HGF values in order to predict the results of therapy for pneumonia was investigated in this study. In a prospective multicenter study we investigated the serum levels of HGF and CRP before and within 48 h after treatment in 70 patients with pneumonia. Serum levels of HGF before treatment were significantly higher than the HGF levels of a normal population (p < 0.0001). Within 48 h serum HGF levels had decreased significantly in those patients who ultimately responded to the initial antibiotic therapy (p < 0.0001). Serum HGF levels at 48 h were unchanged or increased in cases in whom the initial therapy was ineffective and had to be changed. CRP and HGF levels were significantly correlated. Using multivariate logistic regression analysis it was found that individual changes in acute serum HGF levels and serum HGF levels obtained within 48 h could predict the results of therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP levels were known and used by the physician to decide whether or not to change the initial therapy. We conclude that serial control of serum HGF levels can be used as an early indicator to predict the results of therapy during treatment of pneumonia.

BACKGROUND: Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years.OBJECTIVE: To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers.METHODS: HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented.RESULTS: It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated (r = 0.94, p<0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies.CONCLUSION: This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.

Acute serum levels of hepatocyte growth factor (HGF) were studied in 6 clinical groups with (i) gastroenteritis, (ii) skin and soft tissue infection, (iii) urinary tract infection, (iv) septicemia, (v) influenza, and (vi) chronic hepatitis C in comparison with a normal control group using an enzyme-linked immunosorbent assay method. We found that serum HGF levels were significantly higher in patients with acute infectious diseases (p < 0.0001) compared to patients with chronic viral hepatitis and healthy controls. Serum HGF and CRP levels were correlated significantly, (r = 0.65, p < 10(-7)). We conclude that serum HGF levels are elevated in patients with acute infectious diseases.

The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P < .001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.

In the twelve clinical cases of human granulocytic ehrlichiosis (HGE) so far identified in Scandinavia (ten in Sweden, two in Norway), clinical presentation varied from a mild febrile illness to a severe septic condition with such systemic complications as acute respiratory distress syndrome (ARDS). Laboratory verification was based on PCR (polymerase chain reaction) in ten cases, and on serology in two cases. Sequence analysis of 16S rDNA showed the infectious agents to belong to the Ehrlichia phagocytophila genogroup. Seroprevalence data indicate widespread human exposure to granulocytic Ehrlichia; mean seroprevalence, 15-20% of 1,000 clinical sera from tick-exposed patients (mainly from Sweden and Norway). Proposals for diagnostic criteria and procedures, and case management are presented in the article.

Hepatocyte growth factor (HGF) is a multifunctional growth factor. After lung injury HGF is secreted in the lung and promotes reconstruction of the damaged organ. We measured, retrospectively, the serum HGF concentrations collected on admission in 55 patients with bacterial pneumonia, using an enzyme-linked immunosorbent assay (ELISA). The patients were divided into 3 groups: Group 1 was survivors with normal liver function (n = 14), Group 2 was survivors with abnormal liver function (n = 31) and Group 3 was non-survivors (n = 10). Median concentrations of HGF were elevated in Groups 1 and 2; and no statistically significant difference between these 2 groups was found. Group 3 had a median HGF concentration within the reference range, significantly lower than both Group 1 and Group 2. In addition LDH was significantly higher in non-survivors as compared with survivors. The combination of LDH and HGF concentrations discriminated between survivors and non-survivors (sensitivity 0.90 and specificity 0.96). The results support the hypothesis that increased levels of HGF might be a natural part of the healing process of lung injury, irrespective of liver involvement, and that patients without increased HGF levels, especially those with concomitant liver function impairment, may have a poor prognosis.

Community-aquired pneumonia caused by atypical bacteria or viruses was studied in a double-blind trial comparing fleroxacin 400 mg od and doxycycline 100 mg bd for 10 days. The aetiology was confirmed in 258 of 411 cases (66%), of which 133 were caused by Mycoplasma spp., Chlamydia spp. or Legionella spp.; 30 patients had viral infection, nine had pneumococcal or Haemophilus influenzae infection and 93 had mixed aetiology. In intention-to-treat analyses clinical response rates in fleroxacin-treated patients were 86% (157/182) and 75% (137/182) 2-8 days and 3-5 weeks after therapy, respectively. Corresponding results with doxycycline were 93% (177/191) and 85% (162/190), respectively. Differences between treatments seemed to be due to the lower activity of fleroxacin compared with doxycycline against mycoplasma and pneumococci. Drug-related adverse events were reported in 39% of 204 fleroxacin patients and in 34% of 207 doxycycline patients. The null hypothesis that fleroxacin was <15% inferior to doxycycline was accepted at early follow-up but rejected at later review.

Candida glabrata is a well-known cause of lower urinary tract infections. Systemic infections caused by this organism are less common, but have increased dramatically in recent years. Prosthesis infection caused by C. glabrata is extremely rare. We report a case of prosthesis failure due to C. glabrata 5 y after candidaemia and pyelonephritis caused by this organism. The same C. glabrata strain was isolated from both infections, as confirmed by the random amplified polymorphic DNA (RAPD) method.

Properdin is a component of the alternative activation pathway of the complement system. Deficiency or dysfunction of the protein is inherited in an X‐linked recessive manner. Affected males have an increased risk of developing meningococcal disease. Six multi‐generation families with different types of properdin deficiency were analyzed using microsatellite and other polymorphisms on the X chromosome. Based on multipoint data, it was found that the disease gene maps close to DXS255 (Z max = 13.3 at θ max = 0.00) and DXS426 (Z max = 12.9 at θ max = 0.00) on the Xp‐arm near the centromere. There was no indication of genetic heterogeneity among the six families analyzed. Thus it is now possible to perform accurate DNA‐based determination of the inheritance of the mutation in affected families.

Two cases of campylobacter septicaemia are described. The first, caused by Campylobacter laridis was associated with gastroenteritis and occurred in a healthy individual. In the second case, a catalase negative species, C. mucosalis was isolated from blood in an immunocompromised patient with symptoms of pneumonia. Both campylobacter strains grew faintly under the routine culture conditions used. Improved diagnostic procedures for Campylobacter species may thus be warranted.

Granulocyte‐mediated reactions such as opsonization, chemotaxis, and release of granulocyte myeloperoxidase and lactoferrin were studied in properdin‐deficient and normal human serum incubated with serogroup A and W‐135 meningococci. There were no differences between the sera when serogroup A meningococci were studied. Opsonic and chemotactic activity were impaired against serogroup W‐135 meningococci in properdin‐deficient serum. Restitution with properdin restored both activities. We found similar release of myeloperoxidase and lactoferrin from granulocytes challenged with serogroup A or W‐135 meningococci in either sera. These findings are in accordance with the clinical observations of meningococcal infections caused by serogroup W‐135 in properdin‐deficient patients as well as the absence of infections caused by serogroup A meningococci.

A late prosthetic valve endocarditis due to Actinobacillus actinomycetemcomitans and Staphylococcus epidermidis in a 72-year-old man is reported. A simple indirect immunofluorescence technique was used to confirm the etiological diagnosis. This test may be useful when diagnostic problems occur in infections with microorganisms of uncertain pathogenic importance.

Neisseria meningitidis serogroup W-135 appears to be a fairly common cause of infection associated with properdin deficiency or dysfunction, and anticapsular antibodies might be protective in these patients. For this reason, bactericidal and opsonophagocytic activities for serogroup W-135 were investigated before and four weeks after vaccination of two properdin-deficient adults with tetravalent meningococcal vaccine. In addition, the response of IgM, IgG and IgA class antibodies to the serogroups A, C, Y and W-135 was determined by ELISA. There was no evidence of poor antibody responses in the properdin-deficient persons. Vaccination promoted classical pathway-mediated killing in serum and opsonization of serogroup W-135 to the same extent as that seen in vaccinated controls. The increase of alternative pathway-mediated killing in the properdin-deficient sera was moderate, but vaccination clearly enhanced alternative pathway-mediated opsonophagocytosis in the sera. It was also shown that vaccination markedly reduced the requirement for properdin in alternative pathway-mediated killing of the meningococci.

The influence of purifiedStaphylococcus aureus lipase on granulocyte function and morphology was studied. The lipase itself was strongly chemotactic; in addition preincubation of granulocytes with low concentrations of lipase enhanced the directed movement, as assayed in the agarose system. Higher concentrations of lipase, in contrast, gave a progressive reduction of granulocyte chemotaxis; at 12µg lipase per ml, cells were almost immobilized. Phagocytic killing ofStaphylococcus aureus by granulocytes preincubated with lipase was reduced in a dose-dependent manner. At 12µg lipase per ml almost no staphylococcal killing occurred. This was mainly accounted for by a reduction of bacterial uptake, but some decrease in intragranulocytic killing was also noted. These functional alterations, which can all be ascribed to an interference with membrane functions, were associated with marked changes of the granulocyte surface structure, which was denuded and lacked normal microvilli. The effects of lipase were partly retained after heat inactivation of lipase activity, indicating that the effects of staphylococcal lipase on granulocyte function are not due to enzymatic activity alone. These effects of lipase may be an important virulence factor and contribute to the preferential location of lipase-productingStaphyloccus aureus strains at deep sites of infection.

A selective deficiency of properdin (P) was identified in a 58-year-old male and in his 29-year-old nephew, both of whom were clinically healthy. As determined by different immunochemical methods P at low concentrations (about 2 mg/l) was detectable in serum and plasma. Three female relatives, including the mother and daughter of one of the P-deficient males showed moderately low P concentrations. The findings clearly suggested that the deficiency was inherited as an X-linked trait. Three males belonging to another family with P deficiency also showed detectable P concentrations. By contrast, no P (less than 0.1 mg/l) was found in 8 males belonging to three other families. We suggest that there are two variants of X-linked P deficiency: P deficiency type 1, characterized by extremely low P concentrations (less than 0.1 mg/l); and P deficiency type 2 recognizable by P concentrations of about 2 mg/l. The P detected in P deficiency type 2 had subunits of normal molecular weight (52 kilodaltons), but eluted in a lower molecular weight range than did the P of normal serum, either on gel filtration (Ultrogel AcA 22) or on size exclusion chromatography (TSK-4000). The evidence suggested that the P concentration may be one determinant of P oligomer formation. P-deficient serum type 2 did not support fluid phase C3 cleavage in the presence of such alternative pathway activators as inulin and zymosan, nor did it support efficient lysis of guinea pig erythrocytes in agarose gel. By contrast, rabbit erythrocytes were efficiently lyzed, but at a slow rate. P-deficient serum type 1 did not support lysis of rabbit erythrocytes in the assay system used. The reaction was clearly promoted by very low concentrations of purified P. Partially purified P from a male with P deficiency type 2 was shown to be hemolytically active. Further evidence of P function in P deficiency type 2 was obtained by using IgG-presensitized serogroup W-135 meningococci in an alternative pathway-mediated serum bactericidal assay.