History of pyrogens

The
history of pyrogens can be traced to the introduction of intravenous therapy,
in 1656, by Sir Christopher Wren, the awareness of a fever producing agent was
there. The documented research into the development of medicines contains many
references to episodes of fever following intravenous infusions. But the
scientists could not find the mechanism by which intravenous therapy was
producing fever. Since fever frequently followed sepsis in wounds, physicians
thought that the tissues in the wounds were decomposing, then putrefying by
fermentation and in the process were causing the fever (Kelly, 2013).

Louis
Pasteur (1822-1895), discovered that bacteria caused fermentation. Then
scientists associated fever and pyrogens with fermentation and with bacteria.
But they had no idea about the origin of pyrogens, whether they were produced
by bacteria or whether they were a part of bacteria. Research into the nature
of pyrogens started showing good results in 1894, when Centanni extracted
pyrogens from many types of bacteria.
He
extracted pyrogens from Esherichia coli too. Scientists started looking into
the chemical and physiological nature of pyrogens. Centanni showed that
pyrogens were not proteinous and that they were not susceptible to heat. It was
the publications of Hort and Penfold, in the year 1912, that provided the best
understanding of the nature of pyrogens. They started the Rabbit Assay and
standardized it for fever. By correlating the fever effect in rabbits with the
extent of pyrogens, and by characterizing the bacteria by staining as Gram
positive and Gram negative Hort and Penfold could prove that the pyrogenic
bacteria were predominantly Gram negative whereas the Gram positive were mostly
apyrogenic. Then they could correlate in the wounds were decomposing, then
putrefying by fermentation and in the process were causing the fever (Hart,
2008).
Louis
Pasteur (1822-1895), discovered that bacteria caused fermentation. Then
scientists associated fever and pyrogens with permeation and with bacteria. But
they had no idea about the origin of pyrogens, they were produced by bacteria
or whether ere a part of bacteria.
Research
into the nature of pyrogens started showing good results in 1894, when Centanni
extracted pyrogens from many types of bacteria. He extracted pyrogens from
Esherichia coli too. Scientists started looking into the chemical and
physiological nature of pyrogens. Centanni showed that pyrogens were not
proteinous and that they were not susceptible to heat. It was the publications
of Hort and Penfold, in the year 1912, that provided the best understanding of
the nature of pyrogens. They started the Rabbit Assay and standardized it for
fever. By correlating the fever effect in rabbits with the extent of pyrogens,
and by characterizing the bacteria by staining as Gram positive and Gram
negative Hort and Penfold could prove that the pyrogenic bacteria were
predominantly Gram negative whereas the Gram positive were mostly apyrogenic
(Hart, 2008).
Then
they could correlate between the bacterial count in the injected distilled
water and the extent of fever caused and also proves that dead bacteria also
caused fever. Then, Hort and Penfold, concluded that the real cause of
injection fevers was a filterable substance which was stable to heat, and was
produced by bacteria. Seibert’s investigations in the years 1923-1925, proved
these findings conclusively. Seibert could also develop a process for the
production of apyrogenic infusion fluids (Rolla, 2006).
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