Serum Derived Transfer Factor Stimulates the Innate Immune System to Improve Survival Traits in High Risk Pathogen Scenarios.

Preclinical Research Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal to survive high-risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host's cytokine response profile. Mice mortally challenged with 5,000 colony-forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0.01). The splenic bacterial load in untreated mice was over 10,000 times higher than that in the TF treated mice. Twenty-four hours post-administration, the treated murine population expressed a rapid temporal increase in serum IL-6 (26-fold) and INF-γ (77-fold) concentrations. IL-6 can act as a critical signal regulating action against bacterial pathogens. A comparative double-blind study performed using dogs confirmed to be undergoing a canine parvovirus challenge showed that when conventional supportive therapy was supplemented with a single 5 mg TF dose there was a reduction (p ≤ 0.01) in group mortality (68% of the TF treated group survived versus 32% of the placebo group), an observation consistent with the observed increase in INF-γ, a cytokine associated with promoting antiviral activity. Drug Dev Res 78 : 189-195, 2017. © 2017 Wiley Periodicals, Inc.

Exercise performance in children with severe beta-thalassemia before and after transfusion.

UNLABELLED: Thalassemia major is associated with impaired exercise tolerance because of the severe anemia and cardiopulmonary dysfunction characteristic of the condition. OBJECTIVE: To assess the exercise performance in thalassemic children before and two hours after hemotransfusion. PATIENTS AND METHODS: The study included eleven children with thalassemia major (12.3 +/- 2.8 years; Hb g/dl = 8.1 +/- 1.3) and 11 matched controls. All subjects underwent comprehensive pulmonary function assessment and incremental exercise test on a treadmill. RESULTS: The thalassemic children were, in general, shorter and lighter than their healthy counterparts; we also found lower absolute values of lung function parameters which did not reach statistical significances. On the other hand the most considerable differences were found in diffusion capacity (uncorrected TL(L,CO) % = 56.8 +/- 12.1 vs. 94.3 +/- 16.1 in controls; p<0.001) and blood oxygen content (ctO2 mmol.L(-1) = 4.7 +/- 1.1 vs. 8.3 +/- 0.8, p<0.05). The thalassemic children had significantly lower exercise capacity compared to controls (VO2/ kg = 27.1 +/- 5.0 vs. 37.1 +/- 3.2 mL.min(-1).kg(-1); p<0.001). In the patients' group hemoglobin was elevated significantly two hours after transfusion (Hb g/L from 80.5 +/- 12.7 to 93.6 +/- 10.6; p<0.001) leading to significant improvement in exercise duration (7.3 +/- 2.8 vs. 10.3 +/- 2.3 min; p<0.05), VO2/kg (28.5 +/- 5.0 vs. 36.2 +/- 7.1 mL.min(-1).kg(-1); p<0.05), and transfer factor (4.27 +/- 1.40 vs. 5.41 +/- 1.08 mmol.min(-1).kPa(-1); p=0.003). There were strong correlations between Hb and TL(L,CO) and VO2 (r = 0.687 and 0.750, respectively; p < 0.01 for both). CONCLUSIONS: Patients with thalassemia major have a seriously reduced transfer factor and exercise impairment. The short-term changes in hemoglobin concentration are associated with significant improvement in exercise performance.

Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) presenting with haemoptysis.

Respiratory bronchiolitis associated interstitial lung disease is an uncommon condition in current or ex-smokers. The presentation is non-specific, but haemoptysis is uncommonly reported in this condition. We report the case of a 25-year-old woman who presented with significant haemoptysis, dyspnoea, reduced transfer factor and normal clinical examination. In addition, a Medline literature search was performed to review the clinical features and prognosis of this disease. Other causes of haemoptysis were excluded with extensive investigation. The diagnosis was made on thoracoscopic lung biopsy. The patient had significant postoperative complications of prolonged air leak and hydropneumothorax requiring further surgery and prolonged hospital stay. Advice regarding smoking cessation was given. Her pulmonary physiology remains abnormal on follow up but symptoms have improved. Respiratory bronchiolitis-ILD may present with normal examination and radiology. Haemoptysis in this case may have been associated with the underlying disease but could have been incidental. Diagnosis, in general, requires lung biopsy. As in this patient, lung function does not appear to improve significantly on follow up.

Lung function and respiratory health of long-term fiber-exposed stonewool factory workers.

The present study was undertaken to examine the respiratory health of a Danish workforce exposed to man-made vitreous fibers (MMVF) during production. Workers with more than 5 yr occupational exposure to MMVF (n = 377) were compared to a group without MMVF exposure (n = 381). Respiratory health was assessed by questionnaire, dynamic spirometry, and measurement of transfer factor. Overall response rate was 63%. A sample of nonresponders was assessed by questionnaire and spirometry. On most spirometric indices the two groups had comparable values. However, a larger proportion (14.5%) of the exposed subjects had an obstructive flow pattern compared with the control subjects (5.3%). Subgroup analyses showed that the elevated risk of airways obstruction associated with exposure was restricted to heavy smokers. Transfer factor and prevalences of symptoms and self-reported disease were similar in the two groups. There is no indication of excess risk of lung fibrosis. However, a number of exposed workers have some degree of airflow obstruction, which cannot be explained by known confounders. An additive or synergistic action between smoking and fiber exposure on airflow obstruction can be speculated.

[The embryotoxic effect in rats exposed to the blood serum of newborn infants tested for the presence of transfer factors]. / Embriotoksicheskii éffekt u krys pri vozdeistvii syvorotkoi krovi novorozhdennykh detei, testiruemykh na nalichie transfernykh faktorov.

Pregnant rats (day 14 of gestation) received intraamniotic injections of newborn human serum. Transfer factors (TF) present in injected serum produced significant embryotoxic and teratogenic effects, as well as changes in coordination of motor activity (EMG) in newborn rats. The extent of embryological disturbances and the motor activity of 33- to 34-day old recipient rats depend on TF concentration (at serum dilution 1:2) and on the state of infant's motor functions ("normal" group and "risk" group). The results obtained allow to objectively determine the pathogenic effect of serum TF on embryotoxicity and formation of motor coordination in the donor infant.

Repeated measurements of transfer factor in rabbits: an animal model suitable for evaluation of short-term exposure.

Acute temporary changes in lung function may be of use as a biological exposure indicator. However, studies of humans occupationally exposed to complex airborne irritants are often expensive and time demanding. Therefore, an animal model could be a valuable complement. A rabbit model has been evaluated where transfer factor was measured twice during the same day, and with the rabbit awake and available for exposure, in between. Anaesthesia and intubation in 22 rabbits (2.6 [0.2] kg [Mean (SD)]) were immediately followed by two measurements of transfer factor and alveolar volume. Transfer factor was estimated by the single breath CO-technique used in humans. The samples were analysed for CO and He on a gas chromatograph. After one pair of measurements the rabbit was allowed to wake up and after 5 h the duplicate measurements were repeated. The mean values of transfer factor, alveolar volume and transfer constant were 0.50 (0.09) mmol min-1 kPa-1, 127 (8) ml and 3.9 (0.6) mmol min-1 kPa-1 l-1, respectively. The intraindividual coefficients of variation were 7.3%, 5.3% and 6.7%, respectively. Five hours later when the duplicate measurements were repeated, transfer factor, alveolar volume and transfer constant were unchanged still. The results suggest that relatively small changes in transfer factor may be detected without losing power, and thus that this model could be used as a biological exposure indicator.

The relationship between the transfer factor obtained at rest, and arterial oxygen tension during exercise, in patients with miscellaneous pulmonary diseases.

Forty-one consecutive patients with the symptom 'exertional dyspnoea' were referred to the Department of Clinical Physiology for evaluation. Pulmonary fibrosis and chronic obstructive pulmonary disease were the most common diagnoses but other diagnoses were also represented. Some patients had no clinical diagnosis or radiological signs. All patients underwent exercise testing with sampling of arterial blood for blood gas analysis and pulmonary function testing including measurement of the transfer factor (carbon monoxide diffusing capacity) at rest. Independent of spirometric findings and diagnosis a significant correlation (r = 0.80, P < 0.001) was shown to exist between the transfer factor measured at rest and the arterial oxygen tension at maximal exercise level. We recommend measurement of the transfer factor as a screening test for exertional hypoxaemia and suggest that exercise blood gas analysis only seems necessary in patients with a transfer factor between 55% and 80% of the predicted value.

[Frequency of pulmonary function disorders as a function of the degree of sensitization. Studies in a poultry farm]. / Häufigkeit von Lungenfunktionsstörungen in Abhängigkeit von dem Sensibilisierungsgrad. Untersuchungen in einem Geflügelzuchtbetrieb.

20 sensibilized poultry farmers were examined by lung function tests for a 6 years period. Parameters of ventilation, compliance, resistance and the transfer factor did not show any increasing deterioration, but with 3 independent tests changes to an unequal ventilation to moderate small airway obstruction were found.

[A humoral transfer factor preventing rejection of allotransplanted rat liver? (author's transl)]. / Ist der humorale Transferfaktor für die Reaktionslosigkeit von Rattenleberallotransplantaten verantwortlich?

We grafted orthotopically 11 DA and 20 WiS-livers into LEW. The recipients of DA-livers survived 10.5 +/- 4.3 days; of the 20 recipients of WiS-liver, however, nine survived 18-37 days, and the other 11 survived indefinitely. The cells of recipients who survived more than 4 months showed GvHR of grade III, and their transfer showed no significant immunosuppressive effect. The indefinitely surviving liver recipients could accept specific skin grafts, but normally rejected third party skin. The serum of these recipients was able to prolong the survival of kidney grafts. This transfer factor is in our estimation responsible for the prolonged survival of rats with liver grafts.