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Biomedical subjects

K Laitinen

Publications and source records attributed to K Laitinen.

At least 37 records · Page 2Linked to original sources

Carbon assimilation and nitrogen in needles of fertilized and unfertilized field-grown Scots pine at natural and elevated concentrations of CO2.

Effects of elevated CO2 concentration ([CO2]) on carbon assimilation and needle biochemistry of fertilized and unfertilized 25-30-year-old Scots pine (Pinus sylvestris L.) trees were studied in a branch bag experiment set up in a naturally regenerated stand. In each tree, one branch was enclosed in a bag supplied with ambient [CO2] (360 micromol mol(-1)), a second branch was enclosed in a bag supplied with elevated [CO2] (680 micromol(-1)) and a control branch was left unbagged. The CO2 treatments were applied from April 15 to September 15, starting in 1993 for unfertilized trees and in 1994 for fertilized trees, which were treated with N in June 1994. Net photosynthesis, amount and activity of Rubisco, N, starch, C:N ratio and SLA of needles were measured during the growing season of 1995. Light-saturated net photosynthetic rates of 1-year-old and current-year shoots measured at ambient [CO2] were not affected by growth [CO2] or N fertilization. Elevated [CO2] reduced the amount and activity of Rubisco, and the relative proportion of Rubisco to soluble proteins and N in needles of unfertilized trees. Elevated [CO2] also reduced the chlorophyll concentration (fresh weight basis) of needles of unfertilized trees. Soluble protein concentration of needles was not affected by growth [CO2]. Elevated [CO2] decreased the Rubisco:chlorophyll ratio in unfertilized and fertilized trees. Starch concentration was significantly increased at elevated [CO2] only in 1-year-old needles of fertilized trees. Elevated [CO2] reduced needle N concentration on a dry weight or structural basis (dry weight minus starch) in unfertilized trees, resulting in an increase in needle C:N ratio. Fertilization had no effect on soluble protein, chlorophyll, Rubisco or N concentration of needles. The decrease in the relative proportions of Rubisco and N concentration in needles of unfertilized trees at elevated [CO2] indicates reallocation of N resources away from Rubisco to nonphotosynthetic processes in other plant parts. Acclimation occurred in a single branch exposed to high [CO2], despite the large sink of the tree. The responses of 1-year-old and current-year needles to elevation of growth [CO2] were similar.

Carbon Dioxide↗

Clodronate as a cause of aminotransferase elevation.

Adverse events (AEs) associated with bisphosphonates are usually gastrointestinal, but elevation of aminotransferases (alanine and aspartate aminotransferase) has also been described in many cases. The frequency of such elevation is, however, poorly investigated. The Probone study is a continuing phase II trial of 610 osteopenic women randomized for 3 years to receive placebo or clodronate at the following clodronate doses: 65 mg, 400 mg and 800 mg daily, and 400 mg for 15 days out of 90 (intermittent group). During the first study year, gastrointestinal AEs were reported by 20-26% of the patients in the five study groups, but no differences appeared between groups. The high-dose clodronate groups (400 mg and 800 mg daily) had no more hepatic side-effects than the low-dose groups, and no serious AE due to liver disease was reported. These higher doses of clodronate caused, however, a mean alanine aminotransferase (ALT) elevation of 5.4-5.8 U (25-24%) which differed significantly from the change in the placebo group (p = 0.002 and p<0.0001, respectively). In those volunteers with initially normal aminotransferase values the risk ratio for an aminotransferase increase to an above-normal value (compared with the placebo group) during the study year was up to 1.8 in the clodronate 400 mg group and up to 2.5 in the clodronate 800 mg group. Among these groups an elevation above the normal limits occurred in up to 11.7% of the volunteers for aspartate aminotransferase (AST) and up to 17.7% for ALT. The respective percentages in the placebo group were 6.2% and 7. 2%. All analyzed bilirubin values were normal. We conclude that oral clodronate use may elevate serum aminotransferase levels, and that these enzymes most likely come from the liver. This elevation has also been described for several other bisphosphonates. However, clinically significant liver injury is unlikely.

Alanine Transaminase↗

A prospective study of bone loss and turnover after cardiac transplantation: effect of calcium supplementation with or without calcitonin.

Cardiac transplantation exposes recipients to osteoporosis and increased risk of consequent fractures. The purpose of the present study was to examine the magnitude, timing and mechanism of bone loss following cardiac transplantation, and to establish whether bone loss can be prevented by calcium with or without calcitonin. Thirty patients (29 men, 1 woman), aged 26-68 years (mean 48 years), were randomized into three groups of 10 to receive either no additional treatment, oral calcium 1 g twice daily for 12 months or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months. Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA) at the time of transplantation and 6 and 12 months later. Markers of bone formation [serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal propeptide (PICP) and aminoterminal propeptide (PINP)] and resorption [serum type I collagen carboxyterminal telopeptide (ICTP)], as well as serum testosterone in men, were assayed before transplantation and at 1 week and 1, 3, 6 and 12 months after transplantation. During the first 6 post-transplant months BMD calculated as a percent change from baseline decreased in the control group by 6.4% (p = 0.014) in the lumbar spine, by 6.0% (p = 0.003) in the femoral neck, by 5.0% (p = 0.003) in the trochanter and by 5.5% (p = 0.130) in Ward's triangle. Between 6 and 12 months a further decline in BMD occurred only at the three femoral sites, ranging from 2.2% to 9.8% (p = 0.004-0.079). In comparison with the control group, the group receiving calcium alone lost less bone in the trochanter between 0 and 6 months (p = 0.019), and the group receiving calcium together with calcitonin lost less bone in the femoral neck (p = 0.068) and Ward's triangle (p = 0.076) between 0 and 12 months. Seven (28%) of 25 assessable patients experienced vertebral compression fractures. Calcium with or without calcitonin had no effect on changes in biochemical parameters; consequently, the three study groups were combined. The markers of bone formation increased, the elevations in mean values being 59% for B-ALP at 1 month (p = 0.009), 152% for PICP at 1 week (p < 0. 0001) and 27% for PINP at 1 week (p = 0.021). After a temporary decline at 3 months B-ALP (p = 0.0002) and PINP (p < 0.0001) at 1 year were nearly doubled compared with baseline values. Throughout the study the marker of bone resorption, serum ICTP, was above normal, with a peak (mean values 67-69% above baseline) at 1 week (p = 0.0002) to 1 month (p < 0.0001). The mean concentration of total testosterone was decreased by 48% (p < 0.0001) 1 week and by 28% (p = 0.0005) 1 month after transplantation, but this was mainly explained by the concomitant drop in serum albumin. High bone turnover underlies bone loss after cardiac transplantation. Bone loss is most rapid during the first 6 post-transplant months. In the upper femur this bone loss may be reduced by treatment with calcium and calcitonin.

Adult↗

A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin.

Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. They were randomized to receive either no additional treatment (n = 22), or oral calcium 1 g twice daily for 12 months (n = 12) or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n = 10). Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P < 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P = 0.027), PICP by 40% (P < 0.0001) and PINP by 63% at 6 weeks (P < 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P < 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P = 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.

Administration, Inhalation↗

Detection of Pneumococcus from whole blood, buffy coat and serum samples by PCR during bacteremia in mice.

Whole blood, purified leukocyte fraction and serum were investigated as specimens for the detection of pneumococcal bacteremia by polymerase chain reaction (PCR) in mice. The PCR findings were compared to the blood culture results. Samples were taken from animals 3 and 12 h after intraperitoneal bacterial challenge. The pneumococcal culture was positive in 27% and 77% of blood samples at 3 and 12 h after challenge, respectively. All whole blood samples were positive by PCR at both time points. Of the buffy coat samples, two of the three pools were PCR-positive at 3 h and all pools at 12 h after bacterial challenge. In the serum sample group, only 40% of the sera were PCR-positive at 3 h, while at 12 h 90% of the samples were PCR-positive. According to these results, whole blood seems to be the best specimen for the detection of pneumococcal DNA by PCR in bacteremic mice.

Animals↗

Chlamydia pneumoniae infection in human monocytes.

Chlamydia pneumoniae infection has been associated with cardiovascular diseases in seroepidemiological studies and by demonstration of the pathogen in atherosclerotic lesions. It has the capacity to infect several cell types, including monocyte-derived macrophages, which play an essential role in the development of atherosclerosis. However, the persistence of C. pneumoniae in mononuclear cells is poorly understood. To study the morphology and biological characteristics of the infection, human peripheral blood monocytes were infected with C. pneumoniae. Freshly isolated monocytes resisted the development of infectious progeny, and confocal and transmission electron microscopy showed that the morphology of the inclusions and chlamydial particles was abnormal. Addition of tryptophan or antibodies against gamma interferon did not diminish the inhibition of C. pneumoniae, suggesting that other factors are involved in the chlamydiostatic activity of the monocytes. Chlamydial mRNA was expressed at least 3 days after infection, however, and a capability for infected monocytes to induce a positive lymphocyte proliferative response was detected for up to 7 days, indicating that C. pneumoniae remains metabolically active in the monocytes in vitro. These results are in accordance with the hypothesis that C. pneumoniae may participate in the maintenance of local immunological response and inflammation via infected monocytes and thus enhance atherosclerosis.

Cells, Cultured↗

Detection of Chlamydia pneumoniae by colorimetric in situ hybridization.

Chlamydia pneumoniae causes chronic infections, which have been associated with cardiovascular diseases. The antigenic structures of the organism have been detected in atherosclerotic lesions by immunohistochemistry. We wanted to further evaluate the presence and localization of C. pneumoniae in different tissues by in situ hybridization. We established a new colorimetric in situ hybridization method using a digoxigenin-labelled probe and studied the localization of C. pneumoniae in formalin-fixed, paraffin-embedded lungs of infected mice. We also used the method to study its presence in 12 abdominal aortic aneurysms. In C. pneumoniae-infected mice, the organism was first detected in bronchial epithelial cells, and later in pneumocytes and endothelial cells. C. pneumoniae was also present in five of eight abdominal aortic aneurysms previously shown to be positive by immunohistochemistry. The findings are in accordance with the invasive nature of C. pneumoniae, and confirm its presence in abdominal aortic aneurysms.

Animals↗

No change of brain extracellular catecholamine levels after acute catechol-O-methyltransferase inhibition: a microdialysis study in anaesthetized rats.

Catechol-O-methyltransferase inhibitors have been newly introduced as adjunct drugs to the levodopa/dopa decarboxylase inhibitor therapy in Parkinson's disease. When given alone, catechol-O-methyltransferase inhibitors seem to affect behaviour. We wanted to determine whether the concentrations of free amine would be increased by catechol-O-methyltransferase inhibition with tolcapone and underpin the positive behavioural effects. To this end, dopamine and noradrenaline levels were analyzed in the microdialysis perfusion fluid collected from several brain regions in chloral hydrate anaesthetized rats. We also analyzed the turnover rate of catecholamines in the brain after single doses of tolcapone and entacapone using the alpha-methyl-p-tyrosine method. On their own, tolcapone (at 10 or 30 mg/kg) did not elevate dopamine or noradrenaline levels in any brain region studied although the formation of catechol-O-methyltransferase-dependent metabolites was strongly reduced. Neither tolcapone nor entacapone (at 30 mg/kg) affected the turnover rate of catecholamines. It seems that catechol-O-methyltransferase inhibitors do not alter behaviour by elevating extracellular levels of free catecholamines levels but other explanations are needed.

3,4-Dihydroxyphenylacetic Acid↗

Brain histamine H3 receptors in rats with portacaval anastomosis: in vitro and in vivo studies.

The long-term effects of portacaval anastomosis (PCA) on histamine H3 receptors in rat brain were studied by in vitro and in vivo methods. The overflow of histamine from the anterior hypothalamus and from cortex after long-term PCA was determined by in vivo microdialysis. The binding properties of [3H]-R-alpha-methylhistamine in membranes from cortex, cerebellum, and rest of brain (ROB) were examined with saturation binding experiments. The regional distribution of [3H]-R-alpha-methylhistamine binding sites in the brain of sham- and PCA-operated rats was assessed also with autoradiography. The tissue levels of histamine were significantly elevated in cortex and ROB of PCA-operated rats. In addition, the spontaneous and K+-evoked overflow of histamine from anterior hypothalamus, and the thioperamide-induced overflow from both anterior hypothalamus and cortex were increased after chronic PCA. In spite of the significantly elevated tissue concentrations and the moderate increase in histamine release, the binding properties of [3HI-R-alpha-methylhistamine to cortical membranes were not significantly changed. However, the autoradiography study did reveal a decrease in [3H]-R-alpha-methylhistamine binding density, particularly in striatum and cortex, where H3 receptors are located mainly at non-histaminergic neurons. In conclusion, we suggest that there is a region-selective increase in the histaminergic activity in chronic PCA, which leads to the down-regulation of somadendritic and pre-synaptic H3 receptors located at non-histaminergic neurons. At the same time, the autoreceptor mediated control of histamine neuronal activity via pre-synaptic H3 receptors located at histaminergic neurons is preserved after long-term PCA.

Animals↗

Animal models for Chlamydia pneumoniae infection.

Animal models are used extensively in the ongoing investigation of a possible causal link between Chlamydia pneumoniae infection and conditions such as asthma and cardiovascular disease. Respiratory infections have been studied in monkeys, while mouse and rabbit models have been used to study both respiratory and cardiovascular infections. The degree of disease induced in mice depends on the strain used, the virulence of the C. pneumoniae strain used, and the dose administered. A characteristic mononuclear pneumonitis occurs, although the infection is systemic and the agent is found outside the lungs, in the circulation, spleen and liver. The infective dose used in the model tends to produce persistent infection, with inflammation continuing after the agent can no longer be cultured from the lungs. In reinfected animals the titre of infective chlamydia in lungs is much diminished, but the inflammation can be quite marked. The continuous persistence of the agent can be demonstrated by polymerase chain reaction (PCR), or, in chronically infected animals, after immunosuppression with cortisone. New Zealand White (NZW) rabbits provide an experimental model, not only for lung infections, but also for C. pneumoniae-induced atherosclerosis. Three laboratories have now reported that after inoculation, plaques develop in the arterial walls of experimental animals on a normal diet. In addition, one laboratory has reported from their studies on atherosclerosis in apoE-deficient and normal mice, that the persistence of the agent in aortic walls could be seen. Further studies are needed to evaluate the effect of the strain of chlamydia and dosage used, the importance of reinfection, the effect of diet and the effect of antibiotic treatment in these models.

Animals↗

Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy.

OBJECTIVE: To study whether levothyroxine (LT4) suppressive therapy exposes patients with differentiated thyroid cancer (TC) to an increased risk of osteoporosis. DESIGN AND METHODS: Markers of bone formation (serum alkaline phosphatase (ALP), osteocalcin (OC), type I procollagen carboxyterminal (PICP) and aminoterminal (PINP) propeptide) and resorption (serum type I collagen carboxyterminal telopeptide (ICTP) and urine hydroxyproline (HOP)), as well as serum intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25(OH)2-D) were measured in 29 patients (25 women, 4 men) with a median age of 45 years, and in 38 age- and sex-matched controls. In a subgroup of 14 patients the measurements were repeated after 5 weeks' interruption of LT4 therapy. Since the primary treatment of TC the patients had used TSH suppressive doses of LT4 (a mean daily dose of 215 microg) for 9 to 11 years. The bone mineral density (BMD) of patients and controls was measured by dual energy X-ray absorptiometry. RESULTS: When on T4 therapy, patients had significantly higher mean levels of ALP (+21%, P < 0.05), OC (+35%, P < 0.01), PICP (+10%, P < 0.05), PINP (+46%, P < 0.001), ICTP (+21%, P < 0.05), and HOP (+37%, P < 0.001) compared with controls. After stopping treatment, OC (-42%, P < 0.001), PINP (-7%, P < 0.05), and ICTP (-54%, P < 0.001) decreased, whereas PICP (+24%, P < 0.001) and 1,25(OH)2D (+29%, P < 0.01) increased. BMD of the lumbar spine and the upper femur was similar in patients and controls. CONCLUSIONS: Patients with differentiated TC have high bone turnover when on LT4 suppressive therapy, After withdrawing treatment both bone formation and resorption decrease acutely. During development of hypothyroidism, serum PICP and PINP, which form from the same type I procollagen molecule and should change similarly, behaved differently. This may be due to different effects of hypothyroidism on their removal through separate receptors in the liver.

Adult↗

Effects of short-term treatment with clodronate on parameters of bone metabolism and their diurnal variation.

The goal of the present study was to answer the question whether the diurnal variation of markers of bone turnover is abolished by inhibition of osteoclasts by bisphosphonates and to assess the effects of short-term treatment with clodronate on parameters of calcium and bone metabolism. Nine healthy, postmenopausal women, all aged 68 years, were studied before and after oral administration of clodronate, first 800 mg daily for 2 weeks and then 1600 mg daily for 2 weeks. During the two-study sessions of 24 hours, the subjects received exactly similar meals and were recumbent from 10:00 P.M. to 6:00 A.M. Blood was sampled every 2 hours and urine was collected in 4-hour aliquots. On each study occasion, three markers of bone resorption (ICTP, serum type-I collagen carboxyterminal telopeptide; F-Pyr, urinary-free pyridinoline; and NTx, crosslinked N-telopeptide of type I collagen) and one marker of bone formation (PICP, serum type I procollagen carboxyterminal propeptide) showed a diurnal variation; only that of NTx was lessened by treatment with clodronate. Mean area under curve (AUC) values for the 24-hour study periods decreased by 41% (P = 0.0002) and 4.7% (P = 0.016) for urinary NTx and F-Pyr, but remained unchanged for serum ICTP (P = 0.41) and PICP (P = 0.99). Treatment with clodronate decreased mean AUC for the serum concentration of total calcium by 1.4% (P = 0.030) and that for the urinary excretion of calcium by 33% (P = 0.021). Mean AUC for serum-intact PTH increased by 19% (P = 0.004). We conclude that short-term treatment with clodronate lowers serum and urine calcium levels and causes compensatory hyperparathyroidism. Treatment also clearly decreases the urinary excretion of NTx and lessens its diurnal variation. As assessed by sensitive markers such as NTx, the nocturnal rise in bone resorption is greatly blunted by inhibition of osteoclasts with bisphosphonates.

Aged↗

Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits.

Chlamydia pneumoniae, a common human respiratory pathogen, has been associated with atherosclerosis in several seroepidemiological studies. Moreover, its presence in lesions of vessel walls has been demonstrated by culture, immunohistochemistry, PCR, and electron microscopy. In this study, we infected intranasally with C. pneumoniae New Zealand White rabbits which had been fed a normal diet. Reinfection was given 3 weeks later. Six of the nine reinfected animals showed inflammatory changes consisting of intimal thickening or fibroid plaques resembling atherosclerosis in 2 to 4 weeks after reinfection. One rabbit had calcified lesions. Immunohistochemistry for C. pneumoniae was strongly positive in the three older affected animals. No lesions were seen in the controls. The results suggest that C. pneumoniae infection is capable of inducing inflammatory atherosclerosis-like changes in the aortas of infected rabbits.

Animals↗

Short-term intravenous bisphosphonates in prevention of postmenopausal bone loss.

This study was performed to test the efficacy of short-term intravenous clodronate and etidronate in the prevention of postmenopausal bone loss. Healthy postmenopausal women, exhibiting a decreasing trend in bone mineral density, were randomized to five groups (clodronate at doses of 150, 300, and 600 mg; etidronate at a dose of 300 mg; and a placebo group) of 21-22 subjects. The drugs were administered intravenously three times with 1-week intervals, followed by regular evaluation for up to 24 months. During the first year, 300 mg of clodronate retarded bone loss significantly in the lumbar spine and femoral neck, where significant protection still persisted after 24 months. Other doses of clodronate (150 and 600 mg) were not bone protective. Etidronate (300 mg) retarded bone loss significantly in the lumbar spine up to 24 months, relative to placebo. Serum concentrations of procollagen I carboxy-terminal propeptide and urinary Ca2+ and hydroxyproline excretion decreased in all bisphosphonate groups during the first month after treatment, but the values returned later toward baseline. In the etidronate-group, serum osteocalcin concentrations also decreased significantly during the first 3 months of the study. Otherwise, no uniform serum responses to bisphosphonate-treatment were detected in circulating markers of bone formation, alkaline phosphatase, or osteocalcin. No significant differences in the serum concentrations of cross-linked carboxy-terminal telopeptide of type I collagen were detected between the groups. Patient acceptance of both bisphosphonates was excellent, and no drug-related adverse side effects were detected. These results suggest that infrequently repeated intravenous treatment with bisphosphonates may effectively counteract postmenopausal bone loss.

Absorptiometry, Photon↗

Pooling of clodronate urinary excretion data: a new pharmacokinetic method to study drugs with highly variable gastrointestinal absorption.

Gastrointestinal absorption of bisphosphonates is highly variable from individual to individual (between-subject variation) and from day to day (within-subject variation), a fact that creates problems both in research and in clinical use of these drugs. We conducted a randomized, two-period cross-over pharmacokinetic (phase I) study to assess the relative bioavailability of two different clodronate preparations: an 800 mg tablet and a 400 mg capsule. Urinary excretion of clodronate correlates with gastrointestinal absorption. To minimize the confounding effect of the high variability of gastrointestinal absorption, we chose as the primary parameter the cumulative amount of clodronate excreted into urine (A(e0-t)) during 9 days (7 days of treatment, 2 days of follow-up). The 90% confidence interval calculated for the population medians of A(e0-t) was 0.83-1.09, well within the 90% confidence interval stipulated for bioequivalence for the area under the curve values (0.80-1.25). This new procedure for pooling urinary excretion data offered a clear advantage over previous methods, and thus could presumably be used to study other drugs as well that are not metabolized and may show highly variable gastrointestinal absorption.

Administration, Oral↗

Animal models for Chlamydia pneumoniae infection.

There is accumulating evidence that persistent Chlamydia pneumoniae infections occur in vivo. Animal studies are necessary in order to evaluate the effects of different treatment regimens for eradication of such infections. A mouse model was found to be efficacious for the study of the effects of cortisone and antimicrobial agents on C. pneumoniae infection.

Animals↗

Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response.

In vitro infection of freshly isolated human peripheral blood mononuclear cells (HPBMC) with Chlamydia pneumoniae was found to induce a production of tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon alpha (IFN-alpha). The secretion was dependent on the amount of infecting chlamydiae and most of it occurred during the first 12 to 24 h. Lipopolysaccharide (LPS) of Salmonella minnesota Rechemotype, used as a positive control for HPBMC activation, induced a release of TNF-alpha, IL-1 beta and IL-6, but not of IFN-alpha, similar to the effect of C. pneumoniae. Viable chlamydiae could not be recovered from HPBMCs infected immediately after their isolation, whereas HPBMCs which were cultured in vitro for 3 to 9 days before infection were able to maintain the growth of C. pneumoniae. Growth inside HPBMCs as well as induction of cytokine response may have a role in the pathogenesis of C. pneumoniae infection.

Chlamydia Infections↗