Procalcitonin and its component peptides in systemic inflammation: immunochemical characterization

Area of Science:

• Biochemistry
• Immunology
• Endocrinology

Background:

• Systemic inflammatory response syndrome (SIRS) and sepsis are generalized responses to injury or infection, often associated with elevated procalcitonin (ProCT) and its aminoterminus peptide (nProCT).
• Serum levels of ProCT and nProCT serve as valuable biomarkers for SIRS/sepsis, aiding in monitoring disease course, therapeutic response, and prognosis.
• This study investigates the serum levels and distribution of ProCT and its component peptides in normal individuals, neuroendocrine cancer patients, and SIRS/sepsis patients.

Purpose of the Study:

• To compare serum levels and distribution of procalcitonin (ProCT) and its related peptides in normal subjects, neuroendocrine cancer patients, and patients with SIRS/sepsis.
• To elucidate the processing and secretion patterns of ProCT and its components in different pathological conditions.
• To evaluate the potential of ProCT and its peptides as diagnostic and prognostic markers for SIRS/sepsis.

Main Methods:

• Utilized region-specific immunoassays, gel filtration, and high-performance liquid chromatography (HPLC) to analyze serum samples.
• Studied pooled and extracted sera from 13 normal subjects, patients with neuroendocrine cancer, and patients with SIRS/sepsis of various etiologies.
• Quantified intact ProCT, nProCT, calcitonin (CT), CT:CCP-I, CCP-I, and calcitonin gene-related peptide (CGRP).

Main Results:

• Normal sera showed measurable levels of intact ProCT, nProCT, CT:CCP-I, CCP-I, mature CT, and CGRP.
• Neuroendocrine cancer sera typically exhibited high levels of these peptides, with significantly increased mature CT (ProCT:CT ratio of 168 ± 68).
• SIRS/sepsis sera demonstrated markedly elevated ProCT, nProCT, and CT:CCP-I in varying proportions, with normal to minimally elevated mature CT (ProCT:CT ratio of 2,900 ± 800) and low CGRP.

Conclusions:

• SIRS/sepsis is characterized by greatly increased ProCT and its peptides due to incomplete post-translational processing, unlike neuroendocrine cancer with high mature CT levels.
• Serum ProCT and nProCT levels are strongly correlated in SIRS/sepsis, with nProCT potentially serving as a more sensitive marker for early or mild cases.
• The hyperprocalcitonemia in SIRS/sepsis is likely cytokine-driven, with the exact cellular origin of this hypersecretion remaining unknown.