Immunogenicity and immunomodulatory activity of bovine surfactant (SF‐RI 1)

Abstract

Respiratory distress syndrome in preterm infants can be treated successfully by endotracheal administration of a bovine surfactant preparation (SF-RI 1). Before the routine use of xenogenic surfactant preparations can be recommended, their immunogenicity as well as their in-vivo and in-vitro immunomodulatory activity have to be investigated. High titers of anti-surfactant antibodies were detected by a sensitive ELISA after immunizing rats, rabbits and mice with SF-RI 1. Repeated endotracheal administration of SF-RI 1 resulted in a humoral antibody response in three out of eight rabbits. After treatment of 34 preterm infants with SF-RI 1 (50-200 mg/kg), a humoral immune response to SF-RI 1 could not be detected. In-vitro restimulation of peripheral blood lymphocytes with SF-RI 1 after primary in-vivo administration did not result in cell proliferation as measured by 3H-thymidine incorporation. SF-RI 1 did not stimulate peripheral blood lymphocytes of neonates in vitro. The mitogenic response of these cells to stimulation with PHA, ConA or PWM was heavily impaired in the presence of SF-RI 1 concentrations increasing from 0.04 to 4 mg/ml. These data indicate that SF-RI 1 is immunogenic and that it may have an influence on lymphocyte proliferation in vivo.

Nebulization of a bovine surfactant in cystic fibrosis: a pilot study

“…Foaming, which might interfere with nebulization, did not develop. Mass output increased linearly with the surfactant concentration (3,6,12,25, 50, 100 mg·mL -1 ) used, whereas the relative recovery decreased (from about 35 to 18%). Most of the losses were due to dried surfactant being trapped against the walls of the nebulizer.…”

“…One patient developed an exacerbation of the pulmonary infection 2 weeks after the completion of the surfactant inhalation period, this being treated with intravenous antibiotics. Whilst healthy normal adults do not usually have measurable serum antibody titres against the hydrophobic surfactant proteins (mainly against SP-B) (<1:10) [25], all but one of the CF patients had elevated levels before therapy (1:20-1:80). No significant changes in serum antibody titres were observed in the patients studied, when assessed at 2 weeks and at 3 months after surfactant therapy.…”

“…Other aliquots were used to determine the SP-B content by a solid phase enzyme-linked immunosorbent assay (ELISA) [24]. The presence of serum antibodies directed against the surfactant proteins SP-B or SP-C was screened in serum samples taken before, and 2 weeks and 3 months after the study, using polyclonal antibodies which had previously been raised in rats against the hydrophobic proteins of the surfactant preparation (Alveofact) [25]. Surface tension was measured in a pulsating bubble surfactometer (Electronetics, Amerherst, NY, USA) at a phospholipid concentration of 3 mg·mL -1 in 0.9% saline with 3 mM CaCl 2 .…”

In vitro modulation of induced neutrophil activation by different surfactant preparations

“…Under pathological conditions leading to respiratory failure, such as immaturity, haemodynamic impairment and inflammation, the close proximity of the vascular bed and alveolar space may, however, favour an undesirable bidirectional protein leak and cell exchange. Plasma proteins and blood cells inactivate surfactant [6][7][8], whilst surfactant preparations and their isolated constituents exert various effects on cell systems involved in the local and systemic immune response [9][10][11][12].…”

Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages

“…By contrast, the hydrophobic surfactant components (phospholipids and SP-B/C) were found to inhibit the respiratory burst of alveolar macrophages and the proliferative T cell responses after challenge with mitogens, allergenic cells, or antigens (5). Predominantly, mixtures of natural or synthetic PC, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) were used, and were shown to be of either inhibitory or stimulatory effect on proliferative lymphocyte responses, or absent an effect, depending on the concentration and composition of the phospholipid classes and their molecular species as well as on the experimental setup (7,8). For instance, alterations in lipid composition caused by interstitial lung diseases, such as sarcoidosis, hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis, led to changes in immunomodulatory properties of surfactants (9,10).…”